Parametrization of Reversible Digitally Filtered Molecular Dynamics Simulations

Adrian P Wiley; Martin T Swain; Stephen C Phillips; Jonathan W Essex; Colin M Edge

doi:10.1021/ct049970t

Parametrization of Reversible Digitally Filtered Molecular Dynamics Simulations

J Chem Theory Comput. 2005 Jan;1(1):24-35. doi: 10.1021/ct049970t.

Authors

Adrian P Wiley^{1

2}, Martin T Swain^{1

2}, Stephen C Phillips^{1

2}, Jonathan W Essex^{1

2}, Colin M Edge^{1

2}

Affiliations

¹ School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, U.K.
² GlaxoSmithKline, New Frontiers Science Park (North), Coldharbour Road, Harlow CM19 5AD, U.K.

PMID: 26641112
DOI: 10.1021/ct049970t

Abstract

Reversible Digitally Filtered Molecular Dynamics (RDFMD) is a method of amplifying or suppressing motions in a molecular dynamics simulation, through the application of a digital filter to the simulation velocities. RDFMD and its derivatives have been previously used to promote conformational motions in liquid-phase butane, the Syrian hamster prion protein, alanine dipeptide, and the pentapeptide, YPGDV. The RDFMD method has associated with it a number of parameters that require specification to optimize the desired response. In this paper methods for the systematic analysis of these parameters are presented and applied to YPGDV with the specific emphasis of ensuring a gentle and progressive method that produces maximum conformation change from the energy put into the system. The portability of the new parameter set is then shown with an application to the M20 loop of E-coli dihydrofolate reductase. A conformational change is induced from a closed to an open structure similar to that seen in the DHFR-NADP(+) complex.