Download MDSA - An interactive analysis tool for Protein Molecular Dynamic

MDSA - An interactive analysis tool for Protein Molecular Dynamic
Simulations: Preliminary Study
1
2
Nurul Adilah Abu Bakar and Siti Zaiton Mohd Hashim , Mohd Shahir Shamsir Omar
1
Software Engineering Department,
Fac. of Computer Science & Info. Systems,
Universiti Teknologi Malaysia,
81310 UTM Skudai, Johor, Malaysia
e-mail: [email protected]
2
Biology Science Department
Faculty of Biosciences and Bioengineering,
Universiti Teknologi Malaysia,
81310 UTM Skudai, Johor, Malaysia
e-mail: [email protected]
Abstract
Molecular dynamics simulation has become an
important tool for predicting and studying
behavior of real materials. Utilisation of
molecular dynamics simulations enabled
researchers to not only decreases the amount of
time to complete a project, but also potentially
decrease the cost of research. One of the most
exciting and difficult challenges in biology is to
understand the interactions of complex
intractable
biological
systems.
Hence,
computational simulations have become
increasingly important in enabling rapid progress
in biological research. Traditionally, many
molecular dynamics simulation software posses
command line interface. Implementation of a
graphical user interface to front end of programs
can simplifly and facilitate molecular dynamics
research compared to the use of command line as
programs input, which is gradually becomes
more difficult for pure biologist as the simulation
complexity increases. This motivated us to
developed MDSA (Molecular Dynamics
Simulation and Analysis), a new strictly
molecular dynamics simulation program written
in JAVA programming language and LINUX
operating system. It offers three-dimensional
interaction and perception. In this paper, we
present the preliminary work of this research i.e.
the review on softwares that have been
accomplished. At the end of this paper, we also
present the future direction of our research that
will be done.
Keywords: Molecular Dynamics Simulation and
Analysis (MDSA), bioinformatics, Graphical
User Interface (GUI)
1. Introduction
One way to understand the
motion in materials is to use computer
simulations method called molecular dynamics.
Molecular Dynamics (MD) is a science of
simulating the motions of a system of particles
and their development with time [1]. These
motions are crucial both in providing useful
insights into motion dependent phenomena and
in the determination and refinement of
macromolecular structures [2].
MD is now one of the principal tools in
the theoretical study of biological molecules.
This computational method calculates the time
dependent behavior of a molecular system. [3].
The use of computer simulations for explorations
of molecular details of biochemical reactions
began in the mid 1970s with simulations of the
initial step in vision and the high-frequency
motions of small proteins
in-vacuo. With
advances in understanding of protein structure,
more realistic simulations were achieved by
solvating the system.
MD allows the study of the behavior
dynamics of a protein as opposed to examining a
snapshot of the protein at a specific time. Atoms
constantly are in motion because of thermal
vibration. The structure of the macromolecule
keeps the atoms in place and restricts their
motion. With MD techniques, protein harmonics
can be analysed and changes in protein
conformation calculated. The increasing need for
obtaining results faster has led to the
development of numerous algorithms that can be
used to simulate molecular dynamics. However,
users often find that the widely used programs
are often too complex and not intuitive enough to
quickly allow training and generate ample
interest in the field.
2. Literature Review
Over the last ten years, many molecular
dynamics simulation software for biological
macromolecule have been developed. But, in this
section, we will initially focus on software that
lacks a graphical interface.
2.1 GROMACS: Groningen Machine
for Chemical Simulations
GROMACS is one of the fastest
molecular dynamics (MD) software vailabe. It is
an open-source software developed by Lindahl
and co-workers [4]. GROMACS supports all the
usual algorithms from a modern molecular
dynamics implementation. It is mainly used to
simulate the dynamics of biochemical such as
proteins and lipids that have complex bonded
and non-bonded interactions. GROMACS is
primarily
designed
for
biological
macromolecules that possess complicated
bonded interactions such as proteins and
carbohydrates. GROMACS is widely used as it
is a comprehensive suite of molecular dynamics
simulation and analysis program.
GROMACS was developed to run on
UNIX based operating systems. The user makes
use of the UNIX shell in order to run programs
and make effective use of this molecular
dynamics simulation package. GROMACS is
considered one of the fastest programs for
molecular
dynamics
simulation
when
benchmarks against AMBER and CHARMM.
However GROMACS is difficult for untrained
biologist to use them intuitively. The command
line input hinder the uninitiated biologists who
are only familiar with the ubiquitous point and
click graphical interface.
2.2 GUIMACS: A Java based front-end for
GROMACS
GUIMACS, a Java-based front-end
programs for the LINUX version of GROMACS.
GUIMACS runs as a standalone application with
Multiple Document Interface (MDI) and enables
its user to run or analyze multiple molecular
dynamics simulations simultaneously. Programs
provided by GROMACS were divided into two
groups. [5] First is GUISim a graphical interface
that includes the user interface window which
runs and manage a basic molecular dynamics
simulation. All the six programs in GUISim were
represented as tabs on
Graphical User
Interface(GUI) window where the user can
choose the various tabs in any order. The second
interface is the GUINalyzer, an interactive front
end interface for programs used for MD analysis.
Although these graphical features are available,
the graphical user interface is very complex and
difficult for untrained biologist to use effectively.
Users must content with a blend of graphic and
command line. Therefore, GUIMACS only
provide a relatively simple interface for novice
LINUX user but not friendly and intuitive for an
unversed or amateur biologist.
2.3 FPV: Fast Protein Visualization Using
Java 3D
Protein visualization methods have also
become an important research area. It is critical
as visualizing structures are important in
biological research. FPV is Fast Protein
Visualization Using Java 3D designed to cater
for this need. This software was developed based
on Java 3D-API for protein visualization system.
It provides the capability for applications to be
run remotely through web browsers. Java 3D is a
scene graph-based 3D application programming
interface (API) for the Java platform. [7]. Java
3D's scene graph-based programming model
provides a simple and flexible mechanism for
representing and rendering scenes. The scene
graph contains a complete description of the
entire scene, or virtual universe. This includes
the geometric data, the attribute information, and
the viewing information needed to render the
scene from a particular point of view.[a] In this
software, this proposed techniques to create
efficient scene graph structures, which allow
loading large molecules (more than 4000 amino
acids) and render them in an acceptable
interactive speed. Using JAVA 3D as a graphic
engine has the advantage because JAVA-3D API
incorporates a high-level scene graph that allows
developers to focus on the objects and the scene
composition.
FPV also presents techniques by
comparing the visualization components of these
systems with two other Java 3D based molecular
simulation tools. For van der Waals display
mode, with the efficient of the scene graph. A
scene graph consists of Java 3D objects, called
nodes, arranged in a tree structure. FPV could
achieve up to eight times improvement in
rendering speed and could load molecules three
times as large as the previous system could. [8].
2.4 JAVA technology in the fields of
bioinformatics
There is growing trend in adopting the
JAVA technology in the fields of bioinformatics
and computational biology [6].
Java has
allowed bioinformatics users to rapidly develop
user-friendly, cross-platform applications that are
accessible to users at all levels of computational
ability.
Traditionally, the language of choice for
bioinformaticians has been Perl. Perl allows the
rapid collection and analysis of data to answer
directed questions, Perl developers can quickly
leverage the power of regular expressions and
the large collection of bioinformatics-based
modules. Furthermore, Perl allows users to
rapidly prototype Internet-based methods for
delivering data. However, the value of
standalone bioinformatics applications created
with Perl is limited in scope in its contribution
back to research biologists. Perl scripts usually
require prerequisite dependency installations and
they lack the dynamic GUI interactions inherent
in Java. For this reason, bioinformaticians have
been using Java to deliver applications to
researchers at all levels of computational ability,
most of whom want to use computational
approaches quickly to supplement other types of
biological work. [9]
Java also features cross-platform
compatibility. By providing a means of mass
viewing any simulation, namely Applet
technology, Java increases this distribution even
more. Applets are components that can be added
to a webpage for easy viewing across the Internet
by means of a web browser. In this way, biology
researchers or students will be able to conduct
the simulations even if they are on others country
or other side.
2.5 iMolTalk: an interactive, internetbased protein structure analysis server.
iMolTalk is a new and interactive web
server for protein structure analysis. It addresses
the need to identify and highlight biochemically
important regions in protein structures. As input,
the server requires only the four-digit Protein
Data Bank (PDB) identifier, of an experimentally
determined structure or a structure file in PDB
format stemming e.g. from comparative
modelling. iMolTalk offers a wide range of
implemented tools (i) to extract general
information from PDB files, such as generic
header information or the sequence derived from
three-dimensional co-ordinates; (ii) to map
corresponding residues from sequence to
structure; (iii) to search for contacts of residues
(amino or nucleic acids) or heterogeneous groups
to the protein, present cofactors and substrates;
and (iv) to identify protein-protein interfaces
between chains in a structure.
The server provides results as userfriendly
two-dimensional
graphical
representations and in textual format, ideal for
further processing. At any time during the
analysis, the user can choose, for the following
step, from the set of implemented tools or submit
his/her own script to the server to extend the
functionality of iMolTalk. [10]
3. Discussion
Molecular dynamics simulations are
relatively inexpensive and powerful capabilities
compared to other computational biology setup
or instrumentation. However, most of them is
difficult to use and offer only limited capabilities
to the untrained biologist. The obstacle here is
the lack of easy to use interface to facilitate
quick training and usage of MD in biological
research.
GROMACS is chosen as it is open source, fast and cluster friendly characteristics.
For GROMACS molecular dynamics software,
all programs in GROMACS utilises a command
line options for input and output files. Effective
use of command line based programs requires
basic knowledge of the UNIX Shell and at least
on of the UNIX based text editors. User must
type the command in a sequential step before
acquiring the final analysis output. Although
GROMACS is a very fast program for molecular
dynamics simulation, it still difficult for pure
biologist or researchers or novice LINUX to use
them efficiently. To solve these problems we
must developed one graphical user interface for
novice LINUX especially pure biologist and
researchers.
The creation of GUIMACS as one of the
Java based front-end for GROMACS did not
solve the interface problems. GUIMACS
eliminates the need for command line input but
replaces this with a plethora of interactive
checkboxes and radio buttons for users. These
checkboxes and radio buttons is complicated as
explanation for their respective role is extremely
insufficient. To solve these problems, we try to
reduce the number of these button and changed
these radio-button and checkboxes with a-user
customizable pop-up menu in graphics display
windows with adequate description of the
options available.
We would also like to implement a
sliding bar to examine the timestep of the
simulation. This would allow a graphical
visualization of the temporal evolution of the
protein during the simulation. A 3D plot of the
residue-time evolution with the root means
square/fluctuation calculation is also desirable
and
would
be
implemented.
Such
implementation would be beneficial to
biologists.
4. Conclusions
Molecular
dynamics
simulation
software (MDSA) is designed to act as a
graphical front end for a molecular dynamics
simulation. It provides intuitive interface for the
untrained biologist and researchers. By
implementing a graphical interface, it would
rapidly enhance interest and accelerate research
in the area of molecular dynamics.
5. Future Work
The continuation of the reseach would
be to continue with our study to further develop
MDSA. Based on the analysis, a working
prototype would be developed, which is design
the three components of the user interface : the
graphics display window, the graphical user
interface windows and the MDSA command
prompt. In the graphic display window, in which
molecules are rendered and interactively rotated,
translated and scaled via mouse controls. A popup menu would also be available.
The graphical user interface (GUI) in
MDSA would include a toolbar that provides
access to the specific tasking form such as
changing the current molecular display
characteristic. The GUI windows would also
provide useful textual information. First it shows
the linearity of the protein structure. The name of
amino acids forming the chain is provided in a
sequence view. The textual information window
also contains information about molecule’s name
and the number of amino acid chain. The amino
acids chain is displayed using one letter
representations of the amino acids. When the
user makes selection on the molecule during the
interaction, the corresponding part of the amino
acids chain in the information window is
highlighted. We plan to include a MDSA
command prompt to provide a command prompt
keyboard input and control for advanced users.
6. References
[1] Karplus, M. and McCammon, J.A. (2002).
Molecular dynamics simulation of biomolecules.
Natl. Acad. Sci. 85,7557-7561.
[2] Karplus, M. and Petsko, G. A. (1990).
Molecular dynamics simulations in biology.
Nature 347, 631-639.
[3] Elber, R. and Karplus, M. (1987). Multiple
conformational states of proteins: a molecular
dynamics analysis of myoglobin. Science 235,
318-321.
[4]
http://www.ch.embnet.org/MD_tutorial/
pages/MD.Part1.html
[5] David van der spoel, Erik Lindah1, Berk
Hess, Gerrit Groenhof, Alan E. Mark, Herman
J.C. Berendsen. Gromacs: Fast, Flexible, And
Free, 2005.
[6] Pradeep Kota, Guimacs - A Java based front
end for Gromacs, Silico Biology 7, 0008, 2006
[7] http://en.wikipedia.org/wiki/Java_3D
[8] C. Tolga, W. Yujun, W. Yuan-Fang, S.
Jianwen. FPV: Fast protein Visualization Using
Java 3D, 2003.
[9] Mohd Shahir Shamsir, Huszalina Hussein,
Siti Zaiton Mohd Hashim and Naomie Salim.
Educating
the
educators:
Incorporating
bioinformatics into biological science education
in Malaysia.
[10] Diemand, AV.; Scheib, H. iMolTalk: an
interactive, internet-based protein structure
analyis server. Nucl Acids Res.
[11] S. Meloan, “Exploring The New Frontier:
Java TM Technology Powers the “Post-Genomic”
Era”, Feature Stories, java.sun.com, September
28, 2001.
[12] http://www.onjava.com/pub/a/onjava/2003/
09/24/java_bioinformatics.html
[13] http://www.jdocs.com/extradocs/126/javax.
media.j3d/doc-files/intro.html
[14] Stephen Smith, Java and Bioinformatics
(for programmers and non-programmers). 2005
[15]
R. A. Sayle and E. J.Milner-White,
“RASMOL: biomolecular graphics for all”,
Trends in Biochemical Sciences, 20(9):374, Sep
1995.
[16] P. J. Kraulis, “MOLSCRIPT: A Program to
Produce Both Detailed and Schematic Plots of
Protein Structures”, Journal of Applied
Crystallography, vol. 24, pp. 946-950, 1991.
[17] R. Koradi, M. Billeter, and K. W¨uthrich,
“MOLMOL: a program for display and analysis
of macromolecular structures”, J Mol Graphics,
14, 51-55, 1996.
[18] W. F. Humphrey, A. Dalke, and K.
Schulten, “VMD – Visual Molecular Dynamics”,
Journal of Molecular Graphics, 14:33-38, 1996.