Exploring free energy surface of oxytocin by using well-tempered metadynamics

Zoran Šućur, Vojtech Spiwok

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

Technická 3, 166 28 Prague 6, Czech Republic

sucurz@vscht.cz

Well-tempered metadynamics (WTmetaD) is one of the enhanced sampling methods for free energy calculations. [1] In this work it was used to explore the free energy surface of neurohypophysial hormone oxytocin, which led to defining different stable conformations of this hormone. The difficulty of choosing the right collective variables (CVs) in the metadynamics as biased simulations was avoided by using dimensionality reduction techinuque - Principal Component Analysis, from the trajectories obtained using unbiased simulations (Molecular dynamics and Replica Exchange Molecular Dynamics). [2] The WTmetaD simulations were done in both implicit (30ns long simulation) and explicit (20ns long simulation) solvent in order to observe their possible impact on the conformation of the molecule. After exploring the free energy surface of oxytocin three distinctive energy minima were found and so we assume that it has three stable conformers.

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).

[1] Barducci A, Bussi G, Parrinello M (2008) Well-Tempered Metadynamics: A Smoothly Converging and Tunable Free-Energy Method. Phys Rev Lett 100,020603.

[2] Spiwok V, Lipovová P, Králová B (2007) Metadynamics in Essential Coordinates:  Free Energy Simulation of Conformational Changes. J Phys Chem B 111, 3073-3076.