Application of Molecular Dynamics Techniques

How can we apply molecular dynamics simulations practically. This section gives a brief outline of a typical MD scenario. Imagine that you are interested in the response of a protein to changes in the amino add sequence, i.e., to point mutations. In this case, it is appropriate to divide the analysis into a static and a dynamic part. What we need first is a reference system, because it is advisable to base the interpretation of the calculated data on changes compared with other simulations. By taking this relative point of view, one hopes that possible errors introduced due to the assumptions and simplifications within the potential energy function may cancel out. All kinds of simulations, analyses, etc., should always be carried out for the reference and the model systems, applying the same simulation protocols. 

A typical molecular dynamics simulation comprises an equflibration and a production phase. The former is necessary, as the name imphes, to ensure that the system is in equilibrium before data acquisition starts. It is useful to check the time evolution of several simulation parameters such as temperature (which is directly connected to the kinetic energy), potential energy, total energy, density (when periodic boundary conditions with constant pressure are apphed), and their root-mean-square deviations. Having these and other variables constant at the end of the equilibration phase is the prerequisite for the statistically meaningful sampling of data in the following production phase. 

Assuming that an equilibrium is now well established, the simulation may be restarted (not newly started) to begin with the sampling of structural and thermodynamic data. In our model case, data acquisition was performed for 3 ns (trajectory data plot not shown). For the production phase, also, the time evolution of the variables mentioned above should be monitored to detect stability problems or con- 

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W Heermann, Computer Simulation Methods in Theoretical Physics, Springer, Berlin, 1986. 

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One of the key advances in computational chemistry during the last quarter of the twentieth century was the development of simulation methods to study motions of atoms and molecules in condensed-phase environments. The paper reviewed here is noteworthy for its pioneering application of molecular dynamics techniques to proteins, and (along with the 1976 Warshel and Levitt paper on lysozyme, discussed elsewhere in this issue) can be considered to herald an increased interest among the computational chemistry community on the problems dealing with the structures and dynamics of biological macromolecules. 

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