SMALL MOLECULE COMPUTATIONAL CHEMISTRY for
COMPUTATIONAL BIOLOGY and MACROMOLECULAR MODELING
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Organizer’s acceptance for participation
Monday, April 13, 2015
S.Aravamudhan Workshop
July 25-30,2011
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Coarse-Grained (Multiscale) Simulations in Studies of Biophysical and
Chemical Systems
Download Full article
Annu. Rev. Phys. Chem. 2011. 62:41–64
Abstract
Recent years have witnessed an explosion in computational power, leading to
attempts to model ever more complex systems. Nevertheless, there remain cases
for which the use of brute-force computer simulations is clearly not the solution. In
such cases, great benefit can be obtained from the use of physically sound
simplifications……………….
1. INTRODUCTION
Workshop on Modeling Biological Systems
Computer modeling of the function of macromolecules and related systems presents a
problem of enormous complexity. Although available computer power has increased rapidly,
there are, nevertheless, still many cases for which the use of brute-force simulations is
clearly not the best approach. Furthermore, there exist many systems whose nature was
correctly elucidated even before the emergence of the current level of computing
power…………...
…………………………….Obviously, this has
enormous difficulties. However, there also exist far less dramatic examples of cases in
which one cannot (and perhaps should not) progress without the use of a simplified
model, and, in fact, recent years have witnessed a growing appreciation of the fact that
the simulation of complex systems, and, in particular, the modeling of biological function,
can greatly benefit from physically sound simplifications.
Monday, April 13, 2015
S.Aravamudhan Workshop
July 25-30,2011
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Beginning with the contents of TEXTBOOK on ORGANIC CHEMISTRY by Morrison and Boyd………..
Neutral water
molecule has a
permanent dipole
moment and
water is a polar
Acidicsolvent
Why only the
zwitterions is
a dipolar ion
and not the
other ions? Alkaline
H2N CHR COOH, the nonionic neutral form does not find much mention: Can there be
equilibrium between zwitterion and the nonionic form at neutral pH?
Monday, April 13, 2015
S.Aravamudhan Workshop
July 25-30,2011
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All atoms are neutral.
Links below are or getting clarifications on the conventions
Atoms covalently bonded in
molecules are considered have the
full share of the one of electron of
the shared pair of electron hence
such atoms are also neutral
-
http://www.youtube.com/user/aram1121944/#p/u/8/LctfaPFRjJ8
http://www.av8n.com/physics/electric-dipole.htm
http://en.wikipedia.org/wiki/DipoleSign convention for dipole
http://hyperphysics.phy-astr.gsu.edu/hbase/electric/dipole.html
has been reversed
http://www.youtube.com/watch?v=513aIefo6QA
| μ | = qd
-
+
Partially covalent bonds between atoms S.Aravamudhan
cause partialWorkshop
charges to be located
Monday, April 13, 2015
and these can give rise to dipole moments; Polar
bonds
July 25-30,2011
+
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Nearly same
energetic
structures but
widely varying
dipole moment
characteristics.
Does this have
a significance
at any stage in
modeling
systems?
Monday, April 13, 2015
Maximum
difference of
6.5 Kcals
mole-1
S.Aravamudhan Workshop
July 25-30,2011
To know the orientation of
dipole moment of water
molecule is simple
enough but as the glycine
molecule finds itself in
varying environments it
would not be all that
simple to estimate its
dipole moment.
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Zwitter ion is a case in which a full unit of positive
charge and negative charge are located at
different ends of the molecule and hence special
reference as dipolar ion.
The nonionic form is more stable. But in
neutral pH, the zwitterionic form
predominates. Indicates the importance of
the stabilization by water medium.
Other categories are cation, anion or polar
molecule where partial charges are created.
Click for computed results
Zwitterion/neut
Nonionic/neut
Difference of about -79.55 KCals per Mole
Monday, April 13, 2015
S.Aravamudhan Workshop
July 25-30,2011
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Since the two neutral forms of the amino acid (Glycine) have small energy
difference, if an input structure corresponds to the guessed structure for
zwitter ionic form, using an abinitio QM method with STO 3G basis set, a
ge4ometrical optimization invariably results in the nonionic neutral form.
http://www.ugc-inno-nehu.com/DBIBT/0_1_Gly_Movie_2.gif
http://www.ugc-inno-nehu.com/DBIBT/0_2_MV_0_45.JPG
In all these what is the importance of Energy? And, When the
structures are nearly of same energy, can electric dipole moment,
be of any consideration?
A few model situations for exemplifying the above consequences
are included in the next slide.
Monday, April 13, 2015
S.Aravamudhan Workshop
July 25-30,2011
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Water dipole
rotated by 180
degrees.
Glycine neutral nonionic str-3 & Water
Note the dipole moment characteristics of these two molecules.
When these two molecules are placed juxtaposed and subjected to optimization,
what would be the consequence?
http://www.ugc-inno-nehu.com/DBIBT/0_3_glyw_opt_movie.gif
Hydrophilic?
During this process how would have the energy varied?
http://www.ugc-inno-nehu.com/DBIBT/0_3_glyw_opt_movie.jpg
The above optimization structure sequence displayed at a faster time scale
http://www.ugc-inno-nehu.com/DBIBT/0_3_glyw_opt_movie_faster.gif
Hydrophobic?
http://www.ugc-inno-nehu.com/DBIBT/0_3_glyw_opt_movie_Wrotated.gif
Monday, April 13, 2015
S.Aravamudhan Workshop
July 25-30,2011
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The way the theoretical calculations display the
movement of water molecule in presence of glycine, could
be the way a drug molecule moves towards the target
macromolecule governed by electrical forces. If the small
molecule moves so in a biological fluid medium, this
would be similar to the way a ship would b e moving in
water current and gets docked at the port. Hence small
molecule gets docked on the macromolecule for favorable
interaction. This word has been used also while virtual
computer aided screening and positioning the small
molecule in the binding site
Note the similar process sequentially when a zwitterion is placed
with water molecule for a geometry optimization
http://www.ugc-inno-nehu.com/DBIBT/0_4_glyzw-w.-opt-mov.gif
Corresponding trends of variation in energy for the
above sequence of structures
http://www.ugc-inno-nehu.com/DBIBT/0_4_glyzw-w-opt-mov.jpg
Monday, April 13, 2015
S.Aravamudhan Workshop
July 25-30,2011
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Spectroscopy can distinguish the cation, anion, neutral
nonionic form and the neutral zwitter ionic forms.
Computational (Quantum Chemical) softwares
provide for calculations of these spectra
theoretically and to compare with experimental
results. A typical calculated results is displayable
from the link below:
http://www.ugc-inno-nehu.com/DBIBT/0_5_sapDnmr-ni-zw-persp.JPG
Even if experimentally the spectra cannot be
obtained for the variety of structures, calculated
pattern and the partial charge distributions can give
valuable information on the trends of electronic
structure variations due to the interactions. This can
be helpful in modeling the system appropriately for
reaching an optimal solutions without too much of
search.
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July 25-30,2011
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The link below is a reproduction from a book on
Biological NMR. The experimental spectral trends have
been reported.
http://www.ugc-inno-nehu.com/DBIBT/0_6_exptal_spectral_trends.JPG
A similar trend as above from computational software
http://www.ugc-inno-nehu.com/DBIBT/0_7_variation_NMR_forGOsequence.JPG
After this much of introduction to theoretical methods for spectroscopic manifestations
during geometrical structure variations…………………
http://www.ugc-inno-nehu.com/DBIBT/0_8_glycine-isomers-water-GO-60pc.JPG
On the role of water there are several publications from Theoretical Biologists who have
investigated using quantum chemical methods. Some of these date back to 1960-70s.
These can be reviewed in the current scenario of Computational Chemistry……….
Getting more information from cluster calculations
http://www.ugc-inno-nehu.com/DBIBT/0_9_File3.pdf
Monday, April 13, 2015
S.Aravamudhan Workshop
July 25-30,2011
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Intermediate Results
in Computational Biology:
Can they be the Realities during
Biological Processes?
S. Aravamudhan
Department of Chemistry
North Eastern Hill University
SHILLONG 793022
Meghalaya: INDIA
Abstract: Workshop on Modeling Biological Systems
This topic has been inspired by the current BIOLOGICAL
applications of Magnetic Resonance Techniques (NMR in particular)
and the advances in Computational Chemistry
Context of my Contributions to IBS Meetings
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S.Aravamudhan Workshop
July 25-30,2011
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http://www.ugc-inno-nehu.com/WMBS/0_Introduction\0_introduction.ppt
http://www.ugc-inno-nehu.com/DBIBT/1_3_File5.pdf
http://www.ugc-inno-nehu.com/WMBS\1_Glycine_GO_NMR\0_Glycine_GO_NMR.ppt
http://www.ugc-inno-nehu.com/DBIBT/1_2_File1.pdf
http://www.ugc-inno-nehu.com/WMBS/2_HydroniumIon/000_Gly_GO_seq_structure.ppt
http://www.ugc-inno-nehu.com/DBIBT/1_1_File2.pdf
http://www.ugc-inno-nehu.com/WMBS/3_Specific_Water_interct_Amino/0_specific.ppt
http://www.ugc-inno-nehu.com/DBIBT/1_4_File4.pdf
If any problems are encountered while downloading the PowerPoint
files, type in the URL: http://www.ugc-inno-nehu.com/WMBS/ in the
browser address bar and find the appropriate web folders and files.
Monday, April 13, 2015
S.Aravamudhan Workshop
July 25-30,2011
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Questions ; Comments ; Remarks
Prof.S.Aravamudhan
Department of Chemistry
North Eastern Hill University
Shillong 793003 Meghalaya
Phone:0364 272 2615
Mobile: 9862053872
Email: inboxnehu_sa@yahoo.com
URL: http://aravamudhan-s.ucoz.com
A link to the facsimile of the
participation certificate
Monday, April 13, 2015
S.Aravamudhan Workshop
July 25-30,2011
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