Computer simulation of conformational change in biological molecules

Abstract

A new method for modifying the course of a molecular dynamics computer simulation is presented. Digitally Filtered Molecular Dynamics (DFMD) applies the well-established theory of digital filters to molecular dynamics simulations, enabling atomic motion to be enhanced or suppressed in a selective manner solely on the basis of frequency. The basic theory of digital filters and its application to molecular dynamics simulations is presented, together with the application of DFMD to the simple systems of single molecules of water and butane. The extension of the basic theory to the condensed phase is then described followed by its application to liquid phase butane and the Syrian hamster prion protein. The high degree of selectivity and control offered by DFMD, and its ability to enhance the rate of conformational change in butane and in the prion protein, is demonstrated.

The DFMD method is then modified and extended to become Reversible Digitally Filtered Molecular Dynamics (RDFMD). The RDFMD method improves the degree of control possible over that of DFMD. DFMD is applied to gas-phase pentane, alanine dipeptide, solvated alanine dipeptide and the pentapeptide YPGDV. In all four systems, RDFMD was able to enhance the rate of conformational change via reasonable transition paths.

Finally, the new method of the Hilbert-Huang Transform (HHT) is described and applied to the analysis of conformational transitions. The HHT is shown to provide clear indications of the changes in energy and frequency during conformational transitions.

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Identifiers

ORCID for Stephen Christopher Phillips: orcid.org/0000-0002-7901-0839

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