TITLE: Avogadro Program for Chemistry Education: To What Extent Can Molecular

Visualization and Three-dimensional Simulations Enhance Meaningful Chemistry Learning?

AUTHOR: Baraa Rayan, Anwar Rayan

SOURCE: Rayan, Baraa & Rayan, Anwar (2017). Avogadro Program for Chemistry
Education: To What Extent can Molecular Visualization and Three-dimensional Simulations
Enhance Meaningful Chemistry Learning? World Journal of Chemical Education, 2017, Vol.
5, No. 4.Retrieved from
https://www.researchgate.net/publication/319016519_Avogadro_Program_for_Chemistry_Ed
ucation_To_What_Extent_can_Molecular_Visualization_and_Three-
dimensional_Simulations_Enhance_Meaningful_Chemistry_Learning

INDEPENDENT VARIABLE/S: Avogadro software

DEPENDENT VARIABLE/S: students’ performance on chemistry exams

BACKGROUND:

Chemistry is a difficult subject, since much knowledge in this field concerns the
molecular level, and students are expected to think on that scale (in terms of interactions
between individual atoms and molecules) to explain phenomena on the macroscopic scale, In
addition, they must link the two-dimensional and three-dimensional structures of molecules
with their physical properties (such as their physical states, boiling and melting points,
density, and color) and their chemical properties (coordination number, chemical stability,
and so forth). All these things should be "cooked" into the mind if one is to understand
chemistry well. During the seventies and eighties, a new era of modeling, molecular
visualization, and three-dimensional simulations was born. Most of these computerized tools
were implemented largely by researchers to help them understand, explain, and predict
chemical phenomena.

There is an increasing recognition of the need to foster teaching approaches that

enhance the quality of student learning, and since learning is a process of making sense of the
topic under study, we presume that teaching chemistry through molecular visualization and
three-dimensional simulation tools may be more effective than traditional approaches. When
teaching chemistry courses in most education colleges, lecturers still use textbooks and two-
dimensional pictures to depict molecules. However, many researchers claim that still pictures
are not adequate for building a mental model of new concepts and phenomena and that
utilizing dynamic pictures is essential to promoting conceptual understanding. Researchers
have found that integrating visual representations such as computerized molecular models,
simulations, and animations into the teaching of science may promote students' understanding
of unobservable phenomena, and afford them the opportunity to make abstract concepts
visible. Manipulating chemical structures in the form of two- and three-dimensional
representations can help students relate the macroscopic, microscopic, and symbolic
representation levels of chemicals to each other, and it can enhance students’ conceptual
understanding and spatial ability.

Science in general and chemistry in particular are taught mostly through direct
instruction involving the delivery of information from the teacher to the student, through
lectures, which involve little student interaction with content. This method of teaching is less
effective and should be revolutionized. Teaching should be linked to learning and should
produce understanding. The information being taught should make sense to the students.
With three-dimensional modeling, we can communicate effectively with students, facilitating
the interactions between them and chemical terms and concepts. Conceptual terms such as
chemical bonding, Van Der Waals (VDW) interactions, polar interaction, π-stacking
interactions, and so forth, will be better understood. Take the concepts of evaporation,
condensation, and boiling as an example. Many students do not understand these ideas. They
lack a conceptual understanding of what happens after water molecules leave a liquid or the
body during the evaporation process, compared to what happens when water molecules leave
a liquid in the boiling process. How is one to explain chemically the sentence "Sweating is
the body's natural way of regulating temperature"? Students may also have difficulty
understanding why water drops form on the outside of a cold drink on a hot summer day. We
believe that one of the secrets of internalizing a concept/term is seeing its relationship to a
phenomenon. To assess conceptual understanding, examinations should include questions or
activities that prompt students to interact intellectually with concepts or terms. They may
need to share some of their own thoughts. This is more likely to result in better assessment of
conceptual understanding. In chemistry, terms such as energy, evaporation, heat, and
corrosion, are labels for concepts. Concepts are fundamental building blocks of thought that
have depth. A concept can become an idea. For example, the concept of condensation
becomes an idea when we associate water vapor in the air reappearing as a liquid when it
comes in contact with a cool object. Converting concepts into ideas is essential to meaningful
learning and conceptual understanding. When students understand a concept well and
successfully internalize it, they can (1) think with the concept, (2) utilize the concept in other
areas, (3) say it in their own words, (4) find an analogy or a metaphor for the concept, and
maybe (5) construct a mental or physical model of the concept. This is what we mean by
conceptual understanding at high levels.

Models in general and three-dimensional models in particular, are frequently

developed with the aim of approximating the real thing, in a form that can be used and
studied in cases when a real situation cannot. Models help students better internalize
concepts, clarify, and explain their ideas. Recently, educators in the field of biology outlined
a proposal [10] to modernize biology education by addressing a conceptual understanding of
key concepts, such as the relationship between structure and function. For this purpose, they
highlighted the necessity of utilizing modeling techniques and molecular dynamics
simulations to illustrate the links between the structure of proteins and their function. In
chemistry, we believe that computerized techniques for molecular visualization and 3D
simulations can play an important role in the training portfolios of students learning to teach
chemistry. In this study, we assess the extent to which incorporating molecular visualization
and 3D simulations into learning chemistry will improve the understanding of conceptual
terms. Table 1 summarizes some of the well-known tools for modeling, molecular
visualization, and 3D simulation.

Developing a favorable attitude in students towards science has often been listed as
one of the important goals of science teaching. Movahedzadeh claims that in order to
motivate students and improve their attitudes toward science, instructors ought to redesign
their traditional courses using a hybrid model (i.e., integrating of some of the conveniences of
online learning with traditional face-to-face instruction in the learning process). We think that
integration of computerized techniques and modeling tools with the traditional face-to-face
instruction
PROBLEM:

Difficulty of the subject Chemistry, since much knowledge in this field concerns the
molecular level, and students are expected to think on that scale (in terms of interactions
between individual atoms and molecules) to explain phenomena on the macroscopic scale, In
addition, they must link the two-dimensional and three-dimensional structures of molecules
with their physical properties (such as their physical states, boiling and melting points,
density, and color) and their chemical properties (coordination number, chemical stability,
and so forth)

OBJECTIVE/S:

The main objective of this study was to examine how integrating tools for molecular
visualization and three-dimensional simulation into chemistry courses at the college level
may affect students’ conceptual understanding of chemistry and their attitudes toward
learning chemistry. In so doing, we can assess the importance of utilizing computerized tools
for molecular visualization and three-dimensional simulation in general, and the Avogadro
program in particular, as they relate to the learning of chemistry in college.

THEORETICAL FRAMEWORK:

INPUT PROCESS OUTPUT

students’
performance on
Poor performance of Avogadro software
students in chemistry exams
chemistry exams
 CONCEPTUAL FRAMEWORK: (Diagram)

Pre test

Control group Experimental group

N=12 Configurations and N=11

polarity

Molecular stability
Traditional AVOGADRO
teaching integration
Intermolecular
interactions and
physical properties

Functional groups in
given organic
compounds

Post test
 METHODOLOGY: (Flowchart/Diagram)

Pre test Avogadro - post test

experimental group

• same exam • Traditional - • same exam

control group

FINDINGS:

 the results show significant differences between the groups in favor

of the experimental group that used Avogadro.
 the average scores and the standard deviations of the experimental
and control groups on the chemistry examinations, with regard to
certain topics related to intermolecular interactions and physical
properties (such as the boiling point/ melting point), molecular
stability, configurations and polarity, resonance and chemical
stability, and functional groups in given organic compounds.
 incorporating Avogadro software into chemistry education may
contribute to increasing students' understanding of chemistry and
improve their performance on examinations
 linking lecture content with hands-on molecular modeling by
Avogadro—namely, seeing and doing—enhances students'
understanding of conceptual chemical terms and provides them with
the necessary skills for three-dimensional visual literacy and for
understanding the linkages between chemical structures at the
microscopic level and physico-chemical properties seen at the
 macroscopic level.
 he use of modeling tools in chemistry education can play a central
role in corroborating what is being learned and bringing scientific
knowledge closer to students.
Introduction

Chemistry is a difficult subject, since much knowledge in this field concerns the molecular
level, and students are expected to think on that scale (in terms of interactions between
individual atoms and molecules) to explain phenomena on the macroscopic scale 1, 2, 3, In
addition, they must link the two-dimensional and three-dimensional structures of molecules
with their physical properties (such as their physical states, boiling and melting points,
density, and color) and their chemical properties (coordination number, chemical stability,
and so forth). All these things should be "cooked" into the mind if one is to understand
chemistry well. During the seventies and eighties, a new era of modeling, molecular
visualization, and three-dimensional simulations was born. Most of these computerized tools
were implemented largely by researchers to help them understand, explain, and predict
chemical phenomena

There is an increasing recognition of the need to foster teaching approaches that enhance the
quality of student learning, and since learning is a process of making sense of the topic under
study, we presume that teaching chemistry through molecular visualization and three-
dimensional simulation tools may be more effective than traditional approaches. When
teaching chemistry courses in most education colleges, lecturers still use textbooks and two-
dimensional pictures to depict molecules. However, many researchers claim that still pictures
are not adequate for building a mental model of new concepts and phenomena and that
utilizing dynamic pictures is essential to promoting conceptual understanding . Researchers
have found that integrating visual representations such as computerized molecular models,
simulations, and animations into the teaching of science may promote students' understanding
of unobservable phenomena 8, and afford them the opportunity to make abstract concepts
visible. Manipulating chemical structures in the form of two- and three-dimensional
representations can help students relate the macroscopic, microscopic, and symbolic
representation levels of chemicals to each other , and it can enhance students’ conceptual
understanding and spatial ability

Science in general and chemistry in particular are taught mostly through direct instruction
involving the delivery of information from the teacher to the student, through lectures, which
involve little student interaction with content. This method of teaching is less effective and
should be revolutionized. Teaching should be linked to learning and should produce
understanding. The information being taught should make sense to the students. With three-
dimensional modeling, we can communicate effectively with students, facilitating the
interactions between them and chemical terms and concepts. Conceptual terms such as
chemical bonding, Van Der Waals (VDW) interactions, polar interaction, π-stacking
interactions, and so forth, will be better understood. Take the concepts of evaporation,
condensation, and boiling as an example. Many students do not understand these ideas. They
lack a conceptual understanding of what happens after water molecules leave a liquid or the
body during the evaporation process, compared to what happens when water molecules leave
a liquid in the boiling process. How is one to explain chemically the sentence "Sweating is
the body's natural way of regulating temperature"? Students may also have difficulty
understanding why water drops form on the outside of a cold drink on a hot summer day. We
believe that one of the secrets of internalizing a concept/term is seeing its relationship to a
phenomenon.

To assess conceptual understanding, examinations should include questions or activities that

prompt students to interact intellectually with concepts or terms. They may need to share
some of their own thoughts. This is more likely to result in better assessment of conceptual
understanding. In chemistry, terms such as energy, evaporation, heat, and corrosion, are
labels for concepts. Concepts are fundamental building blocks of thought that have depth. A
concept can become an idea. For example, the concept of condensation becomes an idea
when we associate water vapor in the air reappearing as a liquid when it comes in contact
with a cool object. Converting concepts into ideas is essential to meaningful learning and
conceptual understanding. When students understand a concept well and successfully
internalize it, they can (1) think with the concept, (2) utilize the concept in other areas, (3) say
it in their own words, (4) find an analogy or a metaphor for the concept, and maybe (5)
construct a mental or physical model of the concept. This is what we mean by conceptual
understanding at high levels.

Models in general and three-dimensional models in particular, are frequently developed with
the aim of approximating the real thing, in a form that can be used and studied in cases when
a real situation cannot. Models help students better internalize concepts, clarify, and explain
their ideas. Recently, educators in the field of biology outlined a proposal 10 to modernize
biology education by addressing a conceptual understanding of key concepts, such as the
relationship between structure and function. For this purpose, they highlighted the necessity
of utilizing modeling techniques and molecular dynamics simulations to illustrate the links
between the structure of proteins and their function 11. In chemistry, we believe that
computerized techniques for molecular visualization and 3D simulations can play an
important role in the training portfolios of students learning to teach chemistry. In this study,
we assess the extent to which incorporating molecular visualization and 3D simulations into
learning chemistry will improve the understanding of conceptual terms. Table 1 summarizes
some of the well-known tools for modeling, molecular visualization, and 3D simulation.

Developing a favorable attitude in students towards science has often been listed as one of the
important goals of science teaching. Movahedzadeh 15 claims that in order to motivate
students and improve their attitudes toward science, instructors ought to redesign their
traditional courses using a hybrid model (i.e., integrating of some of the conveniences of
online learning with traditional face-to-face instruction in the learning process). We think that
integration of computerized techniques and modeling tools with the traditional face-to-face
instruction in chemistry can serve as a good hybrid model.

The main objective of this study was to examine how integrating tools for molecular
visualization and three-dimensional simulation into chemistry courses at the college level
may affect students’ conceptual understanding of chemistry and their attitudes toward
learning chemistry. In so doing, we can assess the importance of utilizing computerized tools
for molecular visualization and three-dimensional simulation in general, and the Avogadro
program in particular, as they relate to the learning of chemistry in college.
Methods

Avogadro is an advanced molecule editor and visualizer, designed for use in computational
chemistry, molecular modeling, bioinformatics, materials science, and other related areas 19.
It can be utilized by students for the molecular visualization and three-dimensional simulation
of molecules; the user can minimize their tertiary structures and view them from every
conceivable angle and perspective (see Figure 1). However, the utility of Avogadro in
chemistry and biology education has not yet been studied.

Avogadro has a friendly graphical interface that can be easily manipulated by the user to
view the structures of molecules from various angles, in three dimensions. It is quite
entertaining for students to create their own varicolored structures, which look good, and this
may prompt them to start asking questions and link structures to properties (see Figure 2 -
Figure 4). This tool can bring students closer to molecules, revealing details at the
microscopic level, and bring them closer to a better understanding of the laws of chemistry,
chemical properties, chemical reactions, and other phenomena of chemistry. For example, the
user can learn via 3D simulations why the trans-2-butene isomer is more stable than the cis-2-
butene isomer (see Figure 2). The aim here is to lead the student to realize that the two-
methyl groups in the cis-isomer are closer, leading to steric strain, while in the trans-isomer,
the two methyl groups are on opposite sides, resulting in no steric interaction. Using the
space-filling model provided by Avogadro can make this better understood. As well, the
surface area of trans-2-butene is larger, and there is a linear correlation between the surface
area of a chemical and its melting point. The melting point of trans-2-butene is -105.5°C,
while the melting point of cis-2-butene is -138.9°C. However, the boiling point of trans-2-
butene is 0.9°C, while boiling point of cis-2-butene is 3.7°C. This is explained by polar-polar
interactions. Trans-2-butene is non-polar, while cis-2-butene is polar. In the solid phase, the
VDW interactions predominate, due to well-order backing and closer contacts, while in the
liquid phase polar-polar interactions predominate, due to less-order backing and lesser
contacts between molecules.
Figure 3 shows how branching affects the boiling point of a compound (a type of correlation
between Van Der Waals interactions and surface area). Being able to visualize the tertiary
structures of isomers illustrates the chemical logic behind the answer. Molecular visualization
by the Avogadro program and three-dimensional simulation of the structures can play a
central role in internalizing the chemical concepts of Van Der Waals and steric interactions.

Drawing chemicals with Avogadro software is very easy. We select the Draw Tool and build
the molecule from atoms and fragments. The number of hydrogen atoms bonded to each
heavy atom can be automatically adjusted to satisfy valency by checking the Adjust
Hydrogens box. Once the molecular structure is complete, we are able to perform a fast
geometry optimization easily by clicking on the Optimize Geometry icon. Alternatively, we
can combine the Auto Optimization tool with the Draw Tool. This is a unique way to
manipulate the molecule, while the geometry is constantly minimized in the background. We
can observe interactively the effects of changing bond orders and adding/removing groups.

Our research population included first-year college students from Al-Qasemi Academic
College who were enrolled in chemistry courses (twenty-two students took part in this
research). They were divided into two equal groups: (a) an experimental group, in which
students used molecular visualization and 3D simulations in chemistry learning, and (b) a
control group, in which students learned chemistry via the traditional approach by observing
two-dimensional pictures in textbooks only, without the aid of computerized tools for
molecular visualization and 3D simulation. It is worth noting that about half of the students
had not studied chemistry before, and none had experience with three-dimensional models or
in silico tools for modeling purposes. This was the first time the students heard about
computerized techniques for modeling chemicals and predicting properties. The division into
groups was done randomly with the use of college admissions data, to ensure that both groups
were very close. As well, students who had studied chemistry before were distributed equally
between the two groups. The experimental group took part in two workshops (two hours
each) to learn the features of the Avogadro program; the control group continued studying
chemistry without the aid of such tools. The dependent variable was students’ performance
on examinations; the independent variable consisted of the methods and strategies for
learning chemistry in a college of education.

Results and Discussion

The aim of the current study was to learn to what extent molecular modeling and three-
dimensional simulations can enhance chemistry learning in colleges of education and
simplify students' understanding of chemistry concepts. As discussed in the introduction,
during the last couple of decades, many computerized tools for molecular visualization and
three-dimensional simulation have been developed and applied mainly by researchers in the
academic and industrial sectors. One of these tools is the Avogadro program. We tested its
incorporation into chemistry teaching and measured how it affects college-students’
understanding of chemistry and their attitudes toward studying science in general, and
chemistry in particular. Comparisons of the students’ performance on the course
examinations for both the experimental and control groups are presented in Table 2; the
results show significant differences between the groups in favor of the experimental group
that used Avogadro.
Table 3 shows the average scores and the standard deviations of the experimental and control
groups on the chemistry examinations, with regard to certain topics related to intermolecular
interactions and physical properties (such as the boiling point/ melting point), molecular
stability, configurations and polarity, resonance and chemical stability, and functional groups
in given organic compounds.

The findings show clearly that incorporating Avogadro software into chemistry education
may contribute to increasing students' understanding of chemistry and improve their
performance on examinations. As well, through this study, we concluded that linking lecture
content with hands-on molecular modeling by Avogadro—namely, seeing and doing—
enhances students' understanding of conceptual chemical terms and provides them with the
necessary skills for three-dimensional visual literacy and for understanding the linkages
between chemical structures at the microscopic level and physico-chemical properties seen at
the macroscopic level. The use of modeling tools in chemistry education can play a central
role in corroborating what is being learned and bringing scientific knowledge closer to
students.

Body
The Avogadro project has developed an advanced molecule editor and visualizer designed for
cross-platform use in computational chemistry, molecular modeling, bioinformatics,
materials science, and related areas. It offers flexible, high quality rendering, and a powerful
plugin architecture. Typical uses include building molecular structures, formatting input files,
and analyzing output of a wide variety of computational chemistry packages. By using the
CML file format as its native document type, Avogadro seeks to enhance the semantic
accessibility of chemical data types.

The work presented here details the Avogadro library, which is a framework providing a code
library and application programming interface (API) with three-dimensional visualization
capabilities; and has direct applications to research and education in the fields of chemistry,
physics, materials science, and biology. The Avogadro application provides a rich graphical
interface using dynamically loaded plugins through the library itself. The application and
library can each be extended by implementing a plugin module in C++ or Python to explore
different visualization techniques, build/manipulate molecular structures, and interact with
other programs. We describe some example extensions, one which uses a genetic algorithm
to find stable crystal structures, and one which interfaces with the PackMol program to create
packed, solvated structures for molecular dynamics simulations. The 1.0 release series of
Avogadro is the main focus of the results discussed here.

Many fields such as chemistry, materials science, physics, and biology, need efficient
computer programs to both build and visualize molecular structures. The field of molecular
graphics is dominated by viewers with little or no editing capabilities, such as RasMol ,
Jmol , PyMOL , VMD , QuteMol , BALLView , VESTA , and XCrySDen [8, 9], among
many others. The aforementioned viewers are all freely available, and most of them are
available under open-source licenses and work on the most common operating systems
(Linux, Apple Mac OS X, Microsoft Windows, and BSD).

The choice of software capable of building chemical structures in three dimensions is far
smaller. There are existing commercial packages, such as CAChe/Scigress , ChemBio3D ,
GaussView , HyperChem , CrystalMaker , Materials Studio , and Spartan , which are
polished and capable of constructing many different types of molecular structures. They are,
however, not available for all operating systems (most of them only run on Microsoft
Windows), and are not easily extensible, customized, or integrated into automated
workflows. Licensing costs can be prohibitive. If the company were to change its direction or
focus, this can lead to a loss of a significant research investment in a commercial product.
Furthermore, in most cases, these programs use custom, proprietary file formats, and
semantic and chemical data can be lost in conversion to other data formats.

The selection of free, open-source, cross-platform, three-dimensional, molecular builders was

quite limited when the Avogadro project was founded in late 2006. Ghemical was one of the
only projects satisfying these needs at the time. Two of the authors (Hutchison and Curtis)
contributed to Ghemical previously, but had found that it was not easily extensible. This led
them to found a new project to address the issues they had observed in Ghemical and other
packages. The Molden application was also available, able to build up small molecules and
analyze output from several quantum codes. However, it suffers from a restrictive license and
it uses an antiquated graphical toolkit, which is not native on most modern operating systems.

Broad goals for the design of a molecular editor were identified following a case study of the
available applications. One of the main issues with both commercial and open-source
applications is a lack of extensibility; many of the applications also only work on one or two
operating systems. The creation of an open and extensible framework that implements many
of the necessary foundations for a molecular builder and visualizer would facilitate more
effective research in this area. Further, the open, standardized Chemical Markup Language
(CML) file format would be used, to secure semantic and chemical data and allow easy
interoperability with other chemistry software.

At the time of writing, it is apparent that other researchers have perceived similar needs.
Several new applications are available today that focus on both building and visualizing
molecular structure. These include CCP1GUI , Gabedit and some highly specific editors such
as MacMolPlt which focus on particular computational packages (i.e., GAMESS-US for
MacMolPlt). Whilst offering many interesting and useful features, these projects suffer from
the same issues centering around effective reuse of existing code, well commented and
documented code, and easy extension to add new features and adapt for specialized areas.

Implementation
The Avogadro project was started in earnest in 2007, and over the first 5 years of
development has been downloaded over 270,000 times , been translated into over 20
languages , and has over 20 contributors . So far, it has been cited over 100 times , including
applications in spectroscopy, catalysis, materials chemistry, theoretical chemistry,
biochemistry, and molecular dynamics, among many others .

From the beginning, the project has strived to make a robust, flexible framework for both
building and visualizing molecular structures. Much of the initial focus has been placed on
preparing input and analyzing output from quantum calculations. Other applications such as
preparing input for MD simulations and visualizing periodic structures will also be presented,
demonstrating the flexibility of the Avogadro platform. The development team has also been
members of the Blue Obelisk movement, following the three pillars outlined by the group:
Open Data, Open Standards, and Open Source .

Software architecture

One area that seems to suffer in many code bases in chemistry is software architecture. This
can lead to less maintainable code, poor code reuse, and a much higher barrier to entry.
Problems were identified in other projects with a view to minimize their impact when
developing Avogadro. Modern software design processes were used in the initial planning
stages of Avogadro, along with the choice of modern programming languages and libraries.

Avogadro has close ties to several other free, cross-platform, open-source projects to reuse as
much code as is practical. These projects include Qt to provide a free, cross-platform
graphical toolkit; Open Babel for chemical file input/output, geometry optimization, and
other chemical perception; Eigen for matrix and vector mathematics; OpenGL/GLSL for
real-time, three-dimensional rendering; and POV-Ray for ray-traced rendering.

Based on the previous experience of the authors and a review of available programs at the
time, several fundamental choices were made. The C++ programming language; the Qt
graphical toolkit; OpenGL for 3D visualization; CMake as the build system; and Open Babel
as the chemical library. Using this combination of languages and libraries requires the project
to be licensed under the GNU GPLv2 [53] license and made openly available to all.
The core of Avogadro is written in portable C++ code with platform-specific differences
abstracted away by Qt, OpenGL, and Open Babel. The CMake build system makes the build
process relatively simple on all supported platforms. Avogadro has been successfully built
and tested on Linux, Apple Mac OS X, and Microsoft Windows in common 32 and 64 bit
hardware architectures.

The Avogadro framework uses the model, view, controller paradigm. The model is
comprised of the core data classes such as Molecule, Atom, and Bond, views are made up of
the engine/display plugins, and controllers are the tools (interactive mouse) and extensions
(non-interactive, form based/menu based). Every plugin has full access to the core data
model, but view and controller plugins are conceptually different; views are responsible for
displaying data and controllers are responsible for modifying/changing data.

Plugins rely on Avogadro’s set of programming interfaces and almost all functionality is
implemented in self contained plugins that are loaded at runtime. The majority of plugins
distributed with Avogadro are written in C++, but the API is also available in the Python
scripting language. This allows for a great deal of choice in how plugins are implemented.
Each plugin is a singleton class that implements a particular set of functions–depending on
the type of plugin–which allows for features to be implemented in a very modular way.

Over the last few years Avogadro development has started to use nightly builds of the latest
version of the code in order to automatically flag issues introduced in new commits. Code
review was also introduced in order to add a review step before new code is merged, along
with softening the line between someone with commit rights and someone without (anyone
can propose and upload a patch, but a small group can choose if/when the patch will be
merged). Some automated testing has been added, but coverage at this point remains
relatively low. API documentation is automatically generated from comments in the code
using Doxygen.

Plugin interface
Avogadro plugins are divided into four different types corresponding to four main classes
that derive from this common base class, specializing their interface for specific activities
(Figure 1). The Avogadro::Color base class defines the virtual interface for applying colors to
atoms, bonds, and other properties. Avogadro::Engine defines the common interface for all
display types in Avogadro: simple ball and stick, Van der Waals visualizations, surfaces, and
force visualizations. The Avogadro::Tool base class provides the interface for all interactive
tools, focusing principally on mouse and keyboard interaction with Avogadro. Examples of
tool plugins include the draw tool used to draw molecules atom by atom, and the navigation
tool used to pan, rotate, and scale the view of the molecule. There are also several specialized
tools such as the alignment tool.

General code architecture of Avogadro. General code architecture of Avogadro, indicating

major plugin interfaces for colors, display engines, tools, and extensions. Red boxes indicate
code dependencies of Avogadro, blue boxes indicate plugin API classes, and green boxes
inidicate examples of each plugin type.

Finally there is the Avogadro::Extension class, which defines the interface for dialog based
plugins. These extensions can interact with the molecule, and are used for a variety of
purposes from molecule properties dialogs to input file generation dialogs for many quantum
codes including NWChem, Gaussian, GAMESS, and others. This class of plugin is also
applied to file import, and network aware extensions querying web databases for structures
given their common name for example.

At start up, several standard directories, which may be customized, are searched for plugins.
The Qt plugin framework is used to check that the plugins have a recent enough version to be
loaded, and the plugin type can be deduced once loaded. The user interface is then populated
with appropriate entries; tools are added to the main toolbar using their embedded icons,
display types are added to the display type list, and menu entries are added for all loaded
extensions.

The tool and display type plugins can both (optionally) provide a dialog for configuring the
plugin. Dialogs are specific to each plugin and integrated into the user interface.

Display plugins are referred to as “engines” internally. Their primary focus is rendering
graphics to the screen. As is the case with most molecular graphics, a large portion of the
geometric primitives are spheres and cylinders, typically used to represent atoms and bonds.
There are many other properties that can be rendered using the display type plugins, for
example, some of the engines also convey information about the underlying data the
geometric primitives represent to allow for the molecule to be edited. Table 1 shows a
summary of the display plugins distributed with Avogadro.

Engines are performance critical as the render functions are called each time a frame is
requested for display. Efficient rendering is also critical since multiple display types can be
combined to form a composite display. For example, ball and stick display overlaid with a
transparent Van der Waals space-filling display and ring rendering to highlight all rings in the
structure. Figure 2 (d) and (f) show two such combinations of multiple display types.
The navigation tool provides basic scene navigation, implementing rotation,panning, tilting,
and zooming support. The initial point of interaction (where the click occurs) changes the
anchor point for navigation; navigation takes place about the center of molecule when
clicking in empty space or about the center of any clicked atom. During interaction, the
navigation tool provides visual cues to show what type of navigation is taking place. The
navigation tool is also used as the default tool if the currently active tool does not handle the
mouse event passed to it.
One of the other central tools is the draw tool, which implements a free-hand molecule
drawing input method supporting keyboard shortcuts, combo boxes, and a periodic table view
to select elements. The user can use the left mouse button to add new atoms or bonds, or click
on the bonds to change their order. The right mouse button can be used to delete atoms or
bonds, and the directional keys can be used in combination with the mouse to quickly
rotate/pan the molecule.

There are also two tools for adjustment of structures (atom or bond centric), a selection tool
supporting standard selection interactions, and an auto-rotate tool that allows users to set the
speed and angles about which to rotate the molecule. The interactive auto-optimization tool
provides a sculpting interaction, where the user can begin a continuous geometry
optimization and switch back to the draw or adjustment tools and change the shape and
structure of the molecule while observing the new structure being optimized. This can also be
combined with the measurement tool to interactively observe bond lengths and angles evolve
as the structure is updated and the geometry minimized. If the optimization tool is turned off,
the measurement tool also allows the user to precisely adjust bond lengths and/or angles
using the adjustment tools.

Extensions
Extensions represent quite a diverse range of plugins including input generation dialogs for
various quantum chemistry codes such as GAMESS, Molpro, NWChem, etc., animation of
the molecule, and visualization of molecular orbitals and electron density. Network aware
extensions allow the user to click on a menu item to fetch by chemical name and search for
“tnt” or “propanol” and have structures returned by the NIH CACTUS Chemical Structure
Resolver service [54]. A summary of the extensions distributed with Avogadro is shown in
Table 3.
Other extensions translate the entire scene to POV-Ray input, and call POV-Ray to render the
molecule using ray tracing techniques to provide higher quality renderings for publication.
Various molecular property dialogs are also implemented as plugins, drawing largely on
Open Babel functionality to provide an overview of the molecule. Cartesian editors, addition
and removal of hydrogens, fragment, SMILES, and peptide insertion are all implemented as
extensions showing up in Avogadro menus. More recently a crystallography extension was
added, giving access to a much wider range to functionality useful to practitioners in that
area, including Miller Plane visualization, slab and surface generation. New builders for
nanotubes, nanoparticles, and DNA are also planned for upcoming releases.

Colors
The color plugins primarily take either double precision numbers or integer values and return
an RGB value. The plugins range from the standard color plugin that takes atomic number
and returns the standard RGB value for that element through to mapping things like partial
change and index to more easily view various aspects of the molecule’s structure.

By defining a plugin interface for coloring atoms, bonds, or residues, developers can easily
offer flexible rendering options to highlight important information without requiring a user to
tediously set colors on specific atoms or functional groups. Default color plugins are listed in
Table 4, illustrating the variety of options. Each plugin is usually only 40-50 lines of C++
code.
Python scripting
Python bindings are provided for all of the core API. Python code can be used in two ways:
the first is the interactive Python terminal, and the second is to write Python plugins;
extensions, tools, or display types. Writing a Python plugin requires the same functionality to
be implemented as a native C++ plugin [55]. The advantage of Python plugins is that it’s
easier to make prototypes since no compilation is required. Python plugins can also easily be
shared with other users.

The Python bindings interface with the PyQt python bindings for the Qt toolkit, which
enables Python code to use all of Qt’s features when writing a plugin. For example, a short
Python script can present a window using Qt and render molecules using Avogadro [56–58].

Avogadro also includes an interactive Python console (Figure 3, which allows users to
directly script and manipulate the Avogadro environment [59].

The graphical user interface

The first thing most people will see is the main Avogadro application window, as shown in
Figure 4. Binary installers are provided for Apple Mac OS X and Microsoft Windows, along
with packages for all of the major Linux distributions. This means that Avogadro can be
installed quite easily on most operating systems. Easy to follow instructions on how to
compile the latest source code are also provided on the main Avogadro web site for the more
adventurous, or those using an operating system that is not yet supported.

The Qt toolkit gives Avogadro a native look and feel on the three major supported operating
systems—Linux, Apple Mac OS X, and Microsoft Windows. The basic functionality
expected in a molecular builder and viewer has been implemented, along with several less
common features. It is very easy for new users to install Avogadro and build their first
molecules within minutes. Thanks to the Open Babel library [51], Avogadro supports a large
portion of the chemical file formats that are in common use. The vast majority of this
functionality has been written using the interface made available to plugin writers, and is
loaded at runtime. We will discuss these plugin interfaces and descriptions of the plugin types
later.

Semantic chemistry
Avogadro has used CML as its default file format from a very early stage; this was chosen
over other file formats because of the extensible, semantic structure provided by CML, and
the support available in Open Babel . The CML format offers a number of advantages over
others in common use, including the ability to extend the format. This allows Avogadro and
other programs to be future-proof, adding new information and features necessary for an
advanced semantically-aware editor at a later time, while still remaining readable in older
versions of Avogadro.

Through the use of Open Babel , a large array of file formats can be interpreted. When
extending Avogadro to read in larger amounts of the output from quantum codes, it was
necessary to devote significant development resources to understanding and adding semantic
meaning to the quantum code output. This work was developed in a plugin, which was later
split out into a small independent library called OpenQube . More recently a large amount of
work has been done by the Quixote project , JUMBO-Converters, and the Semantic Physical
Science workshop to augment quantum codes to output more of this data directly from the
code. Since CML can be extended, it is possible to reuse existing conventions for molecular
structure data, and add new conventions for the additional quantum data.

Building a molecule: atom by atom

After opening Avogadro a window such as that shown in Figure 4 is presented. By default,
the draw tool is selected. Simply left-clicking on the black part of the display allows the user
to draw a carbon atom. If the user pushes the left mouse button down and drags, a bonded
carbon atom is drawn between the start point and the final position where the mouse is
released.

A large amount of effort has been expended to create an intuitive tool for drawing small
molecules. Common chemical elements can be selected from a drop down list, or a periodic
table can be displayed to select less common elements. Clicking on an existing atom changes
it to the currently selected element, dragging changes the atom back to its previous element
and draws a new atom bonded to the original. If the bonds are left-clicked then the bond order
cycles between single, double, and triple. Shortcut keys are also available, e.g., typing the
atomic symbol (e.g., “C-o” for cobalt) changes the selected element, or typing the numbers
“1,” “2,” and “3” changes the bond order.

Right clicking on atoms or bonds deletes them. If the “Adjust Hydrogens” box is checked, the
number of hydrogens bonded to each atom is automatically adjusted to satisfy valency.
Alternatively, this can also be done at the end of an editing session by using the “Add
hydrogens” extension in the build menu.
In addition to the draw tool, there are two tools for adjusting the position of atoms in existing
molecules. The “atom centric manipulate” tool can be used to move an atom or a group of
selected atoms. The “bond centric manipulate” tool can be used to select a bond, and then
adjust all atoms positions relative to the selected bond in various ways (e.g., altering the bond
length, bond angles, or dihedral angles). These three tools allow for a great deal of flexibility
in building small molecules interactively on screen.

Once the molecular structure is complete, the force field extension can be used to perform a
geometry optimization. By clicking on “Extensions” and “Optimize Geometry” a fast
geometry optimization is performed on the molecule. The force field and calculation
parameters can be adjusted, but the defaults are adequate for most molecules. This workflow
is typical when building up a small molecular structures for use as input to quantum
calculations, or publication quality figures.

An alternative is to combine the “Auto Optimization” tool with the drawing tool. This
presents a unique way of sculpting the molecule while the geometry is constantly minimized
in the background. The geometry optimization is animated, and the effect of changing bond
orders, adding new groups, or removing groups can be observed interactively.

Several dialogs are implemented to provide information on molecule properties and to

precisely change parameters, such as the cartesian coordinates of the atoms in the molecule.

Conclusion
We conclude that incorporating modeling tools such as Avogadro software into chemistry
education might be helpful, bringing the microscopic world of molecules closer to students.
The difference in average scores between the two experimental groups (8.2 points for the
experimental group and 6.4 points for the control group) is significant. The students' feedback
following the initiative was positive and encouraging. Other parameters could be tested in
continuation of this study, such as students' attitude toward learning chemistry and inquiry
skills.

Avogadro offers a semantic chemical builder and platform for visualization and analysis. For
users, it offers an easy-to-use builder, integrated support for downloading from common
databases such as PubChem and the Protein Data Bank, extracting chemical data from a wide
variety of formats, including computational chemistry output, and native, semantic support
for the CML file format. For developers, it can be easily extended via a powerful plugin
mechanism to support new features in organic chemistry, inorganic complexes, drug design,
materials, biomolecules, and simulations. Avogadro is freely available under an open-source
license from http://avogadro.openmolecules.net.
Avogadro’s Best Strengths
 It is free and offers many tools
 Lightweight program
 Plotting of orbitals, visualization of calculation results, it’s faster and generally more
stable than other visualization programs.
 Light weight, easy entry, clean GUI, great compatibility
 The interactive geometry optimization is excellent.
 Input generation
 reads quite a variety of inputs formats; easy to learn
 reading several file types, input generation for several programs, opensource
 Lightweight interface, easy to manipulate structures compared to other software, and
a variety of visualization modes (vdw radius is very useful)
 Easy to use; free
 Potential as an interface for QM programs
 Molecular structure manipulation (esp Bond Centric Manipulation)
 Accessibility for my students
 Building molecules
  Rapid drawing that and be converted to many file types
 creating/editing molecules, easy minimalization (at least in Avogadro 1.2, I am not
sure if Avogadro 2 has this feature)
 Simple intuitive use
 Molecular orbital rendering
 Flexibility
Most Needs Improvement
 isosurface visualization, editing optimization, documentation
 Crashes
 show both alpha and beta spin orbitals for unrestricted calculations, show TDDFT
data, improve builder for solid state materials (crashes easily in windows), builder is
in general very cumbersome (compared to Gview e.g.)
 The latest version is lacking a lot of functionality. Molecular editing tools, such as
dihedral rotations are missing. Aligning multiple structures (such as confomers)
would be great. Gridded view of multiple molecules.
 MEP with better colours
 Stability
 Molecule editing
 Visualizing trajectories, rendering
 Stability
 Saving of modified files in different formats and write out Z-matrices, which was
previously available
 It crashes regularly. It is too hard to select and delete segments of the molecule,
especially in Avogadro2.
 input generation and different force fields assignment
 I might be wrong but Avogadro 2 seems to be lacking the constraints feature for force
field optimization which is a useful feature I use very often in the older Avogadro 1.
Also, being able to view conformer ensembles would be useful as I currently rely on
other tools to do that (Jmol)
 Avogadro 2 could handle CIF files and crystal lattice manipulation more smoothly.
It’s better than the previous version but it still has a long way to go.
 Ubuntu 20.04 snap, editing molecules
 Interface
 Molecule building and editing is clunky
 Interface for QM programs
 Stability and ease-of-plugin-development
 Ability to display/view energy calculations from forcefield optimization.
 Fixing of random crashes, Visualisation of ORCA 5 outputs
 stability
 UI/UX Design
 Avogadro 2 should have at least the same features as Avogadro 1.2
 Builder isn’t as good as other programs
 Avogadro 2 lacks some basic features compared to Avogadro 1
 ESP surfaces are terrible! Can we add a density of state feature?
 To be significantly better than vmd in specific areas
References:
https://avogadro.cc/news/community-survey-21/#:~:text=Avogadro's%20Best%20Strengths,-
It%20is%20free&text=Plotting%20of%20orbitals%2C%20visualization%20of,stable
%20than%20other%20visualization%20programs.&text=The%20interactive%20geometry
%20optimization%20is%20excellent.
https://en.wikipedia.org/wiki/Avogadro_(software)
https://avogadro.cc/news/community-survey-21/
Chandrasegaran AL, Treagust DF, & Mocerino M. (2008). An evaluation of a teacher
intervention to promote students’ ability to use multiple levels of representation when
describing and explaining chemical reactions. Research in Science Education, 38(2), 237-
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Dori YJ, & Hameiri M. (2003). Multidimensional analysis system for quantitative chemistry
problems— symbol, macro, micro and process aspects. Journal of Research in Science
Teaching, 40, 278-302.
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skills in a computerized molecular modeling learning environment. Instructional Science, 40,
69-91.
Pappalardo M, Rayan M, Abu-Lafi S, Leonardi M.E, Milardi D, et al. (2017). Homology-
based modeling of rhodopsin-like family members in the inactive state: structural analysis
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Michaeli A, & Rayan A. (2016). Modeling ensample of loop conformations by Iterative
Stochastic Elimination, Letters in Drug Design and Discovery. 13(7): 646-651.