Petr Hošek1, Daniela Toulcová1, Andrea Bortolato2, Vojtěch Spiwok1


1 Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague,

Technická 3, 166 28 Prague 6, Czech Republic,

2 Heptares Therapeutics Ltd, BioPark, Broadwater Road, Welwyn Garden City, Herts, AL7 3AX, UK.



Molecular dynamics simulation is still computationally too expensive to efficiently simulate slow molecular processes such as protein folding or protein-ligand binding. This significantly limits its application in protein design, drug discovery and related fields. Numerous enhanced sampling techniques have been developed to address this problem, including metadynamics [1]. This method uses a bias potential to “flood” free energy minima and to reduce free energy barriers. A parallel variant of metadynamics – multiple walker metadynamics [2] – was developed early after introduction of basic metadynamics algorithm. Multiple walker metadynamics is a parallel version of metadynamics simulation during which all parallels (walkers) share their bias potential. Systems represented by individual walkers are same, only the initial conditions of simulations are different. This allows for efficient simulation in a parallel computing environment.

In this project we introduce a modification of multiple walker metadynamics where individual walkers may represent different, yet similar, systems, for example different mutants of a protein or a protein with different ligands. This can in future become a basis for parallel screening of protein mutants or parallel screening of ligands. Preliminary data on GPCR-ligand docking will be presented.

This project was supported by COST action GLISTEN (CM1207, LD14133). Access to computing and storage facilities of MetaCentrum (LM2010005), CERIT-SC (CZ. 1.05/3.2.00/08.0144) and IT4Innovations Centre of Excellence project (CZ.1.05/1.1.00/02.0070, LM2011033) is greatly appreciated. Participation at the conference is supported by specific university research (MSMT No 21/2014).


1. Laio A., Parrinello M. Proc Natl Acad Sci USA 99 (2002), 12562-12566.

2. Raiteri P., Laio A., Gervasio F.L., Micheletti C., Parrinello M. J Phys Chem B 110 (2006), 3533-3539.