Molecular dynamics simulation is a computational method that analyzes the physical movements of atoms and molecules over time. It works by calculating the acceleration, position, and velocity of atoms in a system using Newton's laws of motion. The forces between atoms are determined from interatomic potential functions, and initial atom velocities are assigned randomly based on temperature using the Boltzmann distribution. The simulation is iterated in small time steps to track how atom positions, velocities, and accelerations change over time. This provides insights into molecular structure, function, and interactions at the atomic scale.

1. Molecular Dynamics Simulation
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2. Computational method for analyzing the
physical movements of atoms and molecules
Molecular Dynamics Simulation
Relating to molecules Study of Motion Imitation of a situation or
process
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3. Computational method for analyzing the physical movements of atoms and molecules
Molecular Dynamics Simulation
Relating to molecules Study of Motion Imitation of a situation or process
Molecular
System
= Atom at initial
stage
= Atom after dT time
3

4. Computational method for analyzing the physical movements of atoms and molecules
Molecular Dynamics Simulation
Relating to molecules Study of Motion Imitation of a situation or process
Molecular
System
= Atom at initial
stage
= Atom after dT time
What do We Want to Know?
1. Acceleration (a)
2. Position (r) and
of Atom “X”
after time dT
Acceleration is a vector. Thus,
direction of a moving particle also
can be known from acceleration.
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5. Computational method for analyzing the physical movements of atoms and molecules
Molecular Dynamics Simulation
Relating to molecules Study of Motion Imitation of a situation or process
Molecular
System
= Atom at initial
stage
= Atom after dT time
What do We Want to Know?
1. Acceleration (a)
2. Position (r) and
of Atom “X”
after time dT
How
Newton’s Second Law:
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6. Computational method for analyzing the physical movements of atoms and molecules
Molecular Dynamics Simulation
Relating to molecules Study of Motion Imitation of a situation or process
Molecular
System
= Atom at initial
stage
= Atom after dT time
What do We Want to Know?
1. Acceleration (a)
2. Position (r) and
of Atom “X”
after time dT
How
Newton’s Second Law: How to Find the Force (F)?
The potential energy is negative
the integral of the force:
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7. Molecular
System
= Atom at initial
stage
= Atom after dT time
What do We Want to Know?
1. Acceleration (a)
2. Position (r) and
of Atom “X”
after time dT
How
Newton’s Second Law: How to Find the Force (F)?
The potential energy is negative
the integral of the force:
For More: https://scripts.mit.edu/~srayyan/PERwiki/index.php?title=Module_7_--_Force_and_Potential_Energy
How to Use this Relationship between
Force (F) and Potential Energy (dU)?
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8. For More:
https://en.wikipedia.org/wiki/Intera
tomic_potential
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9. How to Use this Relationship between
Force (F) and Potential Energy (dU)?
By Using Interatomic Potentials. Interatomic potentials are mathematical functions for
calculating the potential energy of a system of atoms with given positions in space.
Interatomic potentials can be written as a series expansion of functional terms
that depend on the position of one, two, three, etc. atoms at a time.
Then the total potential of the system (Vtot) can be written as
For More: https://en.wikipedia.org/wiki/Interatomic_potential
Where are the Interatomic Potentials in Molecule?
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10. Where are the Interatomic Potentials in Molecule?
A single atom will be affected by the potential energy functions of every atom in the system:
• Bonded Neighbors
• Non-Bonded Atoms (either other atoms in the same molecule, or atoms from different molecules)
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11. Where are the Interatomic Potentials in Molecule?
A single atom will be affected by the potential energy functions of every atom in the system:
• Bonded Neighbors
• Non-Bonded Atoms (either other atoms in the same molecule, or atoms from different molecules)
How to Calculate these HORRIBLE
Interatomic Potentials? 11

12. How to Calculate these HORRIBLE Interatomic Potentials?
Many research group already developed different Force Field
to calculate all these interatomic potential equations
Force field refers to the functional form and parameter sets used
to calculate the potential energy of a system of atoms in
molecular mechanics and molecular dynamics simulations.
For More: https://en.wikipedia.org/wiki/Force_field_(chemistry)
Example of Force Field: AMBER, CHARMM, OPLS, GROMOS
Things to Explore: When to use which Force Field?
Hint: People believe CHARMM forcefield is better for proteins while AMBER
forcefield is better for DNA simulations. (Don’t Depend on People!)
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13. Wait!
At the Starting of the Simulation (When time, t=0),
we know nothing about the atoms (acceleration, potentials) other than their positions. Then
how to calculate the potentials of the molecule after dT time?
Remember:
Solution:
Boltzmann Distribution is used to
assign random potentials to all atoms
that give total potentials of the system
at a certain temperature.
For More: https://en.wikipedia.org/wiki/Boltzmann_distribution 13

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15. DONE!
We have learnt the basic theory about
the Molecular Dynamics Simulation. ☺
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16. DONE!
We have learnt the basic theory about
the Molecular Dynamics Simulation.
☺
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Iterate the Process from Step2. to know
the new position and acceleration after time dT+δ
Now you have new position and acceleration for the atom “X” after time dt
Step 2. Acceleration Calculation
a. Interatomic Potential
Calculation
b. Force Calculation
Step 1. Initial Stage
a. Initial Position b. Boltzman Distribution
Molecular Dynamics Simulation
a. Acceleration b. Position
Just A Recap

17. Why?
•Imagine that an alien lands on Earth, hears about something called a
‘‘bicycle,’’ and wants to understand how it works, how to ride it, and
how to fix it when it breaks.
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18. Why?
•A molecular biologist trying to understand how a protein or other
biomolecule works faces a similar challenge.
An atomic level structure is
tremendously helpful
The atoms in a biomolecule
are in constant motion. Both
molecular function and
intermolecular interactions
depend on the dynamics of
the molecules involved
Unfortunately, watching the
motions of individual atoms
and perturbing them in a
desired fashion is difficult
attractive alternative is to
work with an atomic-level
computer simulation of the
relevant biomolecules
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19. Image: Istvan Kolossvary &
Annabel Todd, D. E. Shaw Research
Protein Folding
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20. Binding of Drugs to their Molecular Targets
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Microsecond to millisecond time frame (This one shows the binding of imatinib, a tyrosine kinase
inhibitor that’s now been approved by the FDA under the name Gleevec, to the BCR/ABL fusion
protein.) Image: Nagar, et al., Cancer Res. 62, 4236 (2002)

21. Mechanisms of Transporter
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22. Practical Considerations in Using MD Simulations
1. Cutoff Methods
• Ideally, every atom should interact with every other atom. This creates a force calculation algorithm of
quadratic order. We may be able to ignore atoms at large distances from each other without suffering
too much loss of accuracy
• Periodic boundary conditions (PBCs) are a set of boundary
conditions which are often chosen for approximating a large
(infinite) system by using a small part called a unit cell.
• PBCs are often used in computer simulations and
mathematical models.
3. Periodic Boundary Conditions (PBCs)
2. Molecules in Solution
• In real situations, a molecule is rarely isolated. In biological systems,
proteins, RNA, and DNA are immersed in a sea of water molecules
• To accurately portray the effect of the solvent molecules on a system,
the solvent molecules must be free flowing.
• How do we establish computational boundaries while keeping a
realistic solvent simulation? (Ans: PBCs)
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23. Canonical ensemble or NVT ensemble: a statistical ensemble where the energy is not known exactly
but the number of particles is fixed. In place of the energy, the temperature is specified.
The canonical ensemble is appropriate for describing a closed system.
A statistical ensemble is a collection of various microstates of an equilibrium macroscopic system
as determined by the constraints operating on the system. The choice of ensemble is dictated by
the nature of the physical system under consideration and properties to be computed.
Statistical
Ensemble
Practical Considerations in Using MD Simulations
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24. Happy Molecular Dynamics Simulating! ☺
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