Pump-probe molecular dynamics (PPMD) simulations in GROMACS and its testing on the PDZ domain

Leona Šerá, Vojtěch Spiwok

Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague, Technická 3, Prague 6, 166 28, Czech Republic

seral@vscht.cz

Despite the fact that allostery plays a crucial role in the protein function, this complicated phenomenon is still not fully understood. Allostery involves gradual changes in the conformation propagating throughout the molecule on the timescales from picoseconds to microseconds. Such action is beyond the capabilities of classical MD. Pump-probe MD is based on the idea that artificial oscillating forces can be applied on selected part of the molecule (pump) and resultant signal transmits across the protein. The residues involved in the dissemination can be identified by employing the Fourier transform (probe). This method was incorporated into GROMACS programme package and different settings were tested on the PDZ domain. If the oscillation is applied on each residue in the separate simulations and all residues in each simulation are probed, it is possible to create the map of allostery, where every residue-residue interconnection should appear. Moreover these data can be statistically analyzed. One PPMD simulation is quite computationally undemanding, since we plan to establish the user-friendly scientific web-portal, where all programs and algorithms would be provided.

This project was supported by COST actions MultiGlycoNano (CM1102, LD13024) and GLISTEN (CM1207, LD14133). Access to computing and storage facilities MetaCentrum (LM2010005) and CERIT-SC (CZ. 1.05/3.2.00/08.0144) is greatly appreciated. Participation at the conference is supported by specific university research (MSMT No 21/2014).