Conformational Free Energy Modelling using Metadynamics

V. Spiwok, B. Králová

Department of Biochemistry and Microbiology, Institute of Chemical Technology Prague

spiwokv@vscht.cz

Molecular dynamics simulation is very important tool of structural biology. Unfortunately, many interesting processes, such as conformational transitions, protein and nucleic acid folding, chemical reactions and others are too slow to be efficiently modelled using conventional simulation techniques. It is also of great interest to predict macroscopic parameters of the system (namely a free energy surface) from microscopic simulations.

Metadynamics methods [1] adds an artificial history-dependent bias potential to the studied system to energetically disfavour its previously visited states. This helps to efficiently explore all possible states of the studied system. Moreover, the bias potential accumulated over the metadynamics run, approximates the free energy surface of the studied system.

Here we present an application of metadynamics in modelling of conformational equilibria of different system. Metadynamics was applied in interpretation of gas-phase spectra of a tripeptide Gly-Phe-Ala [2]. In the field of glycochemistry it was applied in modelling of ring puckering and in modelling of primary hydroxyl group conformations. Conformational equilibria of ubiquitin was studied to compare efficiency of metadynamics with the efficiency of conventional simulations and with the experiment.

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

2. H. Valdes, V. Spiwok, J. Řezáč, D. Řeha, A.G. Abo-Riziq, M.S. de Vries, P. Hobza, Chem. Eur. J., 14 (2008) 4886.

The project was supported by the Ministry of Education, Youth and Sports (MSM 6046137305).