Practical considerations for Molecular Dynamics: Text Books and Additional Resources

Key Points

Force Fields and Interactions

  • Molecular dynamics simulates atomic positions in time using forces acting between atoms

  • The forces in molecular dynamics are approximated by simple empirical functions
Fast Methods to Evaluate Forces

  • The calculation of non-bonded forces is the most computationally demanding part of a molecular dynamics simulation.

  • Non-bonded interactions are truncated to speed up simulations.

  • The cutoff distance should be appropriate for the force field and the size of the periodic box.
Advancing Simulation in Time

  • A good integration algorithm for MD should be time-reversible and energy conserving.

  • The most widely used integration method is the velocity Verlet.

  • Simulation time step must be short enough to describe the fastest motion.

  • Time step can be increased if bonds involving hydrogens are constrained.

  • Additional time step increase can be achieved by constraining all bonds and angles involving hydrogens.
Periodic Boundary Conditions

  • Periodic boundary conditions are used to approximate an infinitely large system.

  • Periodic box should not restrict molecular motions in any way.

  • The macromolecule shape, rotation and conformational changes should be taken into account in choosing the periodic box parameters.
Degrees of Freedom

  • Constraints decrease the number of degrees of freedom

  • Imposing constraints can affect simulation outcome
Electrostatic Interactions

  • Calculation of electrostatic potentials is the most time consuming part of any MD simulation

  • Long-range part of electrostatic interactions is calculated by approximating Coulomb potentials on a grid

  • Denser grid increases accuracy, but significantly slows down simulation
Controlling Temperature

  • On the molecular level, temperature manifests itself as a number of particles having a certain average kinetic energy.

  • Some temperature control algorithms (e.g. the Berendsen thermostat) fail to produce kinetic energy distributions that represent a correct thermodynamic ensemble.

  • Other thermostats, like Nosé-Hoover, produce correct thermodynamic ensembles but can take long to converge.

  • Even though the the Berendsen thermostat fails to produce correct thermodynamic ensembles, it can be useful for system relaxation as it is robust and converges fast.
Controlling Pressure

  • Each barostat or thermostat technique has its own limitations and it is your responsibility to choose the most appropriate method or their combination for the problem of interest.
Water models

  • Continuum models cannot reproduce the microscopic details of the protein–water interface

  • Water–water interactions dominate the computational cost of simulations

  • Good water model needs to be fast and accurate in reproduction of the bulk properties of water
Supplemental: Overview of the Common Force Fields

  • There are different types of force fields designed for different types of simulations.

  • Induction effects are not accounted for by fixed-charge force fields.

  • Using more accurate and diverse target data allows MD force fields to be improved.

Text Books and Additional Resources

Here is a selection of textbooks and other resources that cover molecular dynamics.

While the following resources are listed in no particular order, special consideration should be given to the Living Journal of Computational Molecular Science, which publishes peer-reviewed articles in categories like “Best Practices”, “Tutorials”, “Lessons Learned” as Open Access and aims to updating regularly. Topics range from general Best Practices in Molecular Simulations to more specialized topics like Best Practices for Computing Transport Properties, Best Practices for Quantification of Sampling Quality in Molecular Simulations, Simulation Best Practices for Lipid Membranes, and Lessons Learned from the Calculation of One-Dimensional Potentials of Mean Force.

Glossary

FIXME

barostat
Pressure control algorithms in molecular dynamics (MD) simulations are commonly referred to as barostats and are needed to study isobaric systems. Barostats work by altering the size of the simulation box. Therefore they can only be used in conjunction with periodic boundary conditions (PBC).
ergodicity
In statistical mechanics ergodicity describes the principle that studying a single particle averaged over a long time is equivalent to averaging over many particles which are studied for a short time. See also: “Ergodicity” on Wikipedia
periodic boundary conditions
Periodic boundary conditions (PBC) … See also:
thermostat
Temperature control algorithms in molecular dynamics (MD) simulations are commonly referred to as thermostats and are needed to study isothermal systems. Thermostats work by altering the velocities of particles.

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