Molecular modeling and

Simulations
Harno D Pranowo
Austrian-Indonesian Centre for Computational Chemistry (AIC),
Chemistry Department, Faculty of Mathematics and Natural Sciences,
Gadjah Mada University, Yogyakarta
Definition of Computational Chemistry
Chemistry is the science dealing with construction,
transformation and properties of molecules.

Theoretical chemistry is the sub field where
mathematical methods are combined with
fundamental laws to study processes of chemical
relevance.

Computational chemistry is a collection of
(computer based) techniques for deriving,
representing and manipulating the structures and
reactions of molecules, and those properties that
are dependent on these three dimensional
structures.
Molecular modelling
Molecular modelling studies involve three stages:
Selection of a model; A model is selected to
describe the intra- and inter-molecular
interactions in the system. The two most common
models that are used in molecular modelling are
quantum mechanics and molecular mechanics.

The calculation; such is as energy minimization, a
molecular dynamics or Monte Carlo simulation, or a
conformation search.

Analyzing; The calculation must be analyzed, not
only to calculate properties but also to check that
it has been performed properly
molecular mechanics
ab initio semiempirics Density Functional Theory
electronic structure method
Computational chemistry methods
Computational chemistry methods
Pople Kohn Schrdinger
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IBM 650
CDC 7600
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CRAY Y-MP
CDC 205
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Relative Cost of the Most Powerful
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Simulation Methods for Soft Materials
When Newton meets Schrdinger...
ma F=
+ = +c H

Sir Isaac Newton

(1642 - 1727)
Erwin Schrdinger
(1887 - 1961)
Computational Chemistry and Biology
Electronic Structure
Methods
Classical MD
Simulations
parameter-free MD
ab initio force field
no transferability
problem
chemical reactions
improved optimization
finite T effects
thermodynamic &
dynamic properties
solids & liquids
Computational Chemistry and Biology
Electronic Structure
Methods
Classical MD
Simulations
Force field approach
Ab-initio approach
Character of computational chemistry methods
One of the main problems in
computational chemistry is
selecting a suitable level of
theory for a given problem,
and being able to evaluate the
quality of the obtained
results.
Mixed Quantum-Classical
in a complex environment - QM/MM
Main idea
Partitioning the system into

chemical active part
treated by QM methods

Interface region

large environment that is
modeled by a classical force
field
QM
interface
Classical MM
QM/MM hybrid
APPLICATIONS
I n Situ Simulation of Chemical Reactions I n Situ Simulation of Chemical Reactions
J . Phys. Chem. A,
104, 6464 (2000)
Aqueous Solution
ONOO
-
NO
-
+
1
O
2
PNAS 97 , 10307 (2000)

ONOO
-
+ CO
2
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.
OH +
.
NO
2
ONOOH
Anti-AIDS:
HIV-1 Protease
Prions
and
Metal Ions
DNA-Repair:
Endonuclease IV
Photoisomerization
in Rhodopsin
Molecular Mechanisms
of Apoptosis:Caspase-3
Selectivity of
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HIV- Virus (AIDS)
HIV- I Protease
Asp25
Asp25
Gly27
Gly27
Thr26
Thr26
10ns classical MD simulations
RMS backbone: 0.9
total # of atoms: 24000
Molecular modeling of the crown ether
Selectivity of crown ether
Na
+
-Crown ether Complexes