1. BITS Embryo Lecture Multi-scale modeling and molecular simulations of materials and biological systems
Arthi Jayaraman
Post Doc, University of Illinois Urbana Champaign
Ph.D. North Carolina State University 2006
B.E. Hons (Chemical Engineering) BITS Pilani 2000

2. Outline What is molecular simulation?
Why do we need multi-scale modeling and simulations?
Steps involved in modeling and simulations
Types of models
Brief overview of simulation methods
Examples of systems from
material science
biological science

3. What is molecular simulation?
Molecular simulations use computer models to describe chemical systems at an atomic level of detail
In a computer simulation
Provide individual positions and orientations of every atom or molecule
Place atoms and molecules in a simulation cell
Let them interact with each other through a potential
Let the system evolve according to some simulation algorithm.

4. What is molecular simulation? (contd.)
Example: A gaseous mixture of monoatomic molecules
A-B
B-B
A-A
A-C
B-C
C-C
Components of the system
atom A
atom B
atom C
interaction between species i and j
i-j

5. What is multiscale modeling and molecular simulation?
100 nm
pico sec
1 μm
nano sec
micro sec
Milli sec
length
time
Kremer and Delle Site, Development of methods

6. Why do we need modeling and simulation?
Experiments
cannot study systems at some length scales and time scales
require very expensive equipments to study systems at certain conditions
Modeling and Simulations
allow us to study systems at varying length scales and time scales
are cheaper (computers!)
give us the ability to isolate the effect of each and every parameter involved in the system

7. Steps involved in modeling and simulations
1: What is the system and what do we want to investigate?
How to model the different components of the system
What length scale to use
2: What are interactions between the different components of the system?
What force fields and potentials to use
3: Do we want to study system dynamics or equilibrium thermodynamics?
What simulation method to use
What time scale to use
4: Analysis of the results

8. Types of models Atomistic Coarse grained
Explicitly represent every atom in the molecule C H
Coarse grained
Group of atoms combined together

9. Intermolecular forces and potential
Contributions to potential energy (U) of a system with N molecules
Intramolecular only
Intra- and Inter- molecular only
(between atoms within a molecule)
Repulsion
UvdW - van der Waals
Uel - electrostatic
Upol - polarization
Ustr - stretch
Ubend - bend
Utors - torsion
Ucross - cross
Attraction - + - + - + - +
Dr. D. A. Kofke’s lectures on Molecular Simulation, SUNY Buffalo

10. Brief overview of simulation methods
Monte Carlo
Molecular Dynamics
Specify the initial positions ri(0), and velocities vi(0) of all molecules
Specify the initial positions of all molecules
Solve Newton’s equations Fi = mi ai
Generate random moves for the molecules
Calculate ri(t), vi(t)
Sample with probability  exp(-U/kT)
Take averages
Obtain equilibrium properties
Obtain equilibrium and non-equilibrium properties
Take averages
Dr. Keith Gubbins lectures, NCSU

11. Monte Carlo (MC) versus Molecular Dynamics (MD)
MD gives information about dynamical behavior and equilibrium, thermodynamic properties
so transport properties can be calculated.
MC can only give static, equilibrium properties
In MD the motions of the molecules are natural
(follow newton’s law)
In MC the motions are artificial
(random moves)
Dr. Keith Gubbins lectures, NCSU

12. Brief Overview of Simulation Methods (contd.)
Other simulation methods
Brownian dynamics simulation
Quantum Mechanics-Molecular Mechanics (QM/MM)
Dissipative Particle Dynamics Simulation
Suggested Reading:
– A. R. Leach, Molecular Modelling, Longman, London (1996)
– D. Frenkel and B. Smit, Understanding Molecular Simulation, 2nd ed.,
Academic Press (2002)
– M. P. Allen and D. J. Tildesley, Computer Simulation of Liquids,
Clarendon Press, Oxford (1987)

13. Challenges pick the right model pick the right simulation method
How much detail is required to represent the system accurately and yet have reasonable simulation time ?
(note: too much detail in the model will slow down the simulations tremendously)
pick the right simulation method
Which method would be able to simulate the complete phenomena we are interested in ?
(note: often in some simulation methods the system simply will not equilibrate)

14. Modeling and simulation of confined polymers
A bulk of copolymers confined between surfaces
A-sA
B-sB
Attractive interaction
A12B12 copolymer
A12B12
Using experiments
difficult to make these patterned surfaces (nanometer size patterns)
difficult to study how the polymer organize on these patterned surfaces (observe the organized at the molecular level)
Q. Wang et al. Macromolecules, 33, 4512 (2000);

15. Modeling and simulation of confined polymers
Similar structures found in experiments and simulations
Experiment2
Simulation1
polystyrene-b-polymethylmethacrylate copolymer
A12B12 copolymer
Simulation is able to predict other structures depending on pattern spacing LS
1) Q. Wang et al. Macromolecules, 33, 4512 (2000);
2) L. Rockford et al. Phys. Rev. Lett. 82, 2602(1999)

16. Protein folding
Proteins are large organic compounds made of a sequence of amino acids.
sidechain
amine group
carboxyl group
Before proteins can carry out their important functions, they assemble themselves, or fold
When proteins do not fold correctly (i.e. "misfold"), there can be serious consequences, including many well known diseases, such as Alzheimer's, Mad Cow (BSE), Huntington's, Parkinson's disease, etc.

17. Modeling and simulation of protein folding
Experimental determination of the folded structure is a lengthy and complicated process, involving methods like X-ray crystallography and NMR.
Simulations are trying to predict structures based on the amino acid sequence
There are many ways to model proteins: c H N O
United atom
Atomistic
side group
Coarse-grained
backbone
Carol Hall’s group, NCSU

18. Modeling and simulation of proteins
Two most commonly found motifs in folded proteins
a-helix
b-hairpin
b-turn
Structure of the protein is very complex
Modeling and simulations can be very useful in predicting these complex structures
Dr. Stefan Franzen’s lectures NCSU

19. Summary
Modeling and simulation are a useful tool in understanding the molecular phenomena underlying complex processes in
Material science
Confined polymers, pattern recognition in polymers* micelle formation, phase transitions in materials, colloidal systems, etc.
Biological science
Structure of proteins, DNA and other biopolymers; assembly of proteins; recognition in DNA microarrays* DNA-protein binding, drug design, etc.
Modeling and simulations complement experiments by predicting phenomena that are difficult to study experimentally.
* My PhD thesis