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Chapter 7

Molecular Dynamics

Molecular dynamics
Studies the time
evolution of an energyminimized molecular
system and allows the
prediction of
thermodynamics and
transport properties
directly from the
underlying interactions
between the atoms

MD Simulation Calculation using  Newton’s second law Microscopic information Predictions using  Statistical Mechanics Macroscopic thermodynamics and  transport properties . etc. and transport properties requires statistical mechanics. heat capacities. energy. The conversion of this microscopic information to macroscopic observables such as pressure.. including atomic positions and velocities.Molecular dynamics simulations generate information at the microscopic level.

i. which means that the state of the system at any future time can be predicted from its current state. • Treat the atoms as classical particles. • Molecular dynamics is a deterministic method. EQN: SOLVE NUMERICALLY TO DETERMINE THE TRAJECTORIES OF THE ATOMS ON THE PES . behavior of the system. NEWTON’S EQUATION OF MOTION F = Force on each atom 2 d R F  ma  m 2 dt F  E Pot DIFF.e.• Molecular dynamics calculates the “real” dynamics. from which the time averages of the system’s properties can be calculated.

.Numerical Integration methods Used for solving the previous equation numerically: •Verlet algorithm •Leap-Frog algorithm •Velocity-Verlet algorithm And many more….

Verlet algorithm The most widely used method in molecular dynamics.  repeat time step and present force . It uses the positions for all atoms at time t. and the positions from the previous step at time (t-δt) to calculate the forces at present time and then new positions at time (t+δt) The velocities do not explicitly appear in the Verlet algorithm but they can be calculated t-2t t-t r v F t-t t t+t t t+t Compute new position from  Given current position and  Compute the force at the  Advance to next time step. position at end of previous  current position present and previous positions.

 and  Compute current force Compute velocity at  Advance to next time step.Leap-Frog algorithm The leap-frog method is the variation of Verlet algorithm. It uses the positions at time t. velocities make ‘leap1 frog’ jumps over the positions to give their values at t  t 2 t-2t t-t r v F t-t t t+t t t+t Compute next position Given current position.e.. i. and the velocities from the previous half step at time (t-½δt) to calculate the force at present time t and the velocities at next half step at time (t+½δt) The name of this method comes from its nature. velocity at last half­step next half­step repeat .

  Compute new position Compute velocity at half step Compute force at new position Advance to next time step. velocities and accelerations at the same time t to compute this quantities at later time It does not compromise precision t-2t t-t r v F t-t t t+t t t+t Compute velocity at full step Given current position.Velocity-Verlet algorithm The velocity Verlet algorithm gives positions. and force repeat . velocity.

averages corresponding to experimental observables are defined in terms of Ensemble averages.An experiment is usually made on a macroscopic sample that contains an extremely large number of atoms or molecules sampling an enormous number of conformations. . In statistical mechanics.

pressure (P) and temperature (T) remain constant during the simulation . system volume (V) and potential energy (E) remain constant during the simulation • NVT = number of atoms (N). system volume (V) and temperature (T) remain constant during the simulation • NPT = number of atoms (N).Meaning of Ensembles • NVE = number of atoms (N).

• More useful ensembles include: – Canonical (NVT): requires the particles to interact with a thermostat – Isobaric-Isothermal (NPT): requires the particles to interact with a thermostat and a barostat .MD in different thermodynamic ensembles • MD naturally samples the NVE (microcanonical ensemble): this is not very useful for most applications.

Thermostats • Several possible approaches – Berendsen Method: velocities are exponentially scaled by a factor at each time step so that the system is forced towards the desired temperature – Anderson Method: random collisions take place between the atoms in the system and the heat bath. so that the system is forced towards the desired temperature . so that the system is forced towards the desired temperature – Nosè and Nosè-Hoover: an additional degree of freedom is added to the system.

Barostats • They work similarly to thermostats to control pressure. For example: – Berendsen Method: velocities are exponentially scaled by a factor at each time step so that the system is forced towards the desired pressure .

Trajectory file is saved – Data analysis . PDB files) – You can build it from scratch • Running a simulation – Set up initial configuration – Equilibration phase by doing Molecular Mechanics • System evolves from initial configuration which may not correspond to the energy minimum – Defining simulation length and time per step T – Production phase by running the Molecular Dynamics calculation • Thermodynamic properties of the system are calculated and transport properties predicted. • Choosing initial configuration Needs careful design – very important phase of the experiment – It may come from the experimental data (x-rays.Practical aspects of computer simulations • Setting up a simulation – Define which energy model (force field) should be used to describe atomic interactions.

What is done internally by the program? 1. 3. 5. Given initial positions. initial velocities are assigned Forces on every atom are computed Advance the system by a time step t Recalculate forces and velocities in the new step Repeat the process in the direction of minimal forces CAUTION: ONLY if t is small enough. 2. 4. the output of the simulation is reasonable .

001 .10-12s Amplitude (Å) 0.100 Protein folding Micro to seconds 10-6 .100 .10s 10 .10-6s 1 . angle bending Time scale Femto to pico seconds 10-15 .0.10 Peptide folding Nano to micro seconds 10-9 .1 .1 Collective motion Pico to nano seconds 10-12 .10-9s 0.What  T should I use??? Typical ranges for molecular motion: Description Bond stretching.

1fs – – . 2fs • Both flexible molecules and bonds.Choosing a time step  t • Not too short so that conformations are efficiently sampled • Not too long to prevent wild fluctuations or system ‘blow-up’ • An order of magnitude less than the fastest motion is ideal: Usually bond stretching is the fastest motion: C-H is ~10fs so use time step of 1fs Not interested in these motions? Constrain these bonds and double the time step Suggested time steps: • Rigid Translation. 10 fs • Flexible molecules and rigid bonds.

Running molecular dynamics • An equilibration period is ALWAYS needed – lets system “forget” artificial initial configuration – length of period depends on relaxation time of system Start your MD here Relaxation cycles Production cycles (run a MM calculation first) (this is your MD simulation) .

Calculation of Thermodynamics Properties • Energy • Heat Capacity • Pressure • Temperature .

7) Heat capacity – The heat capacity is formally defined as the partial derivative of the internal energy with the respect to temperature: U   CV     T  (6. .8) V Two ways for calculating CV: • by performing a series of simulations at different temperatures. • from a single simulation by considering the instantaneous fluctuations in the energy. and then differentiating the energy with respect to the temperature.Energy – The internal energy is easily obtained from a simulation as the average of the energies of the states that are examined during the course of the simulation: 1 U E  M M E i 1 i M is the number of steps of the simulation (6.

If there are N particles. then the kinetic energy should equal to 3NkBT/2. the temperature fluctuates. The temperature is directly related to the kinetic energy (K) of the system as follows: N pi 2 k BT K   (3N ) 2 i 1 2mi (6. – In the microcanonical ensemble (NVE).Pressure – The pressure is usually calculated through fij.14) According to the “equipartition theorem” energy of each degree of freedom contributes as kBT/2. and it is whatever you set. the force acting between atoms i and j. . each with three degrees of freedom.13) Temperature – In a canonical (NVT) ensemble the total temperature is constant. then we have the following expression for the pressure: 1 P V   1 N N  Nk BT    rij f ij  3 i 1 j i 1   (6.

Prediction of Time Dependent Properties • Diffusion Coefficient • Velocity Autocorrelation function • Radial distribution function .

Diffusion Diffusion • consider tagging molecules and watching how they migrate (Self-diffusion=Diffusion within a pure substance) Diffusion equations – Combine mass balance with Fick’s law. which gives how concentration is changing with r and t – This can be related to the Mean square displacement (<r2(t)>) .

Interpretation of Diffusion Einstein equation: r 2 (t )  2dDt r2 <r2(t)>= mean square displacement D= diffusion coefficient d = dimension of the movement (d =3 for 3-D movement)  Slope of this    part of the    2dD  curve    – Asymptotic linear behavior of mean-square displacement gives diffusion constant – Independent data can be collected for each molecule t .

v(t)>=VAC(t) Backscattering Time Asymptotic behavior (t) is nontrivial (depends on d) .Velocity Autocorrelation Function (VAC) Definition: VAC gives how the velocity of an atom remains correlated to its initial velocity as time evolves •Typical behavior: VAC Zero slope (soft potentials) Diffusion coefficient is area under the curve:  1 D   d v(0) v ( ) d0 D= diffusion coefficient <v(0).

Calculating the Diffusion Coefficient (D): Two options 1. Using the mean square displacement (<r2(t)>): 1 D 2 2dt r (t ) 2. Using the velocity autocorrelation function (VAC(t)):  1 D   VAC (t ) dt d0 d = dimension of the movement (d =3 for 3-D movement) .

g(r) – key quantity in statistical mechanics – quantifies correlation between pair of atoms • Definition: g(r). if simulating a molecular fluid) at distance r from another atom (or molecule) compared to the ideal gas distribution  ( r ) dr g (r )  id  ( r ) dr Number of atoms at r for ideal gas N  id (r )dr  dr V Number of atoms at r in actual system 4 Hard-sphere g(r) Low density High density dr 3 2 1 0 0 1 2 3 4 5 .Radial Distribution Function • Radial distribution function. gives the probability of finding an atom (or molecule.