Table of Contents
Computational Biology Journal
Volume 2015, Article ID 389018, 9 pages
http://dx.doi.org/10.1155/2015/389018
Research Article

Asymmetric Behavior of Thymidylate Synthase Dimer Subunits in Denaturating Solvent Observed with Molecular Dynamics

1Quantum Chemistry Laboratory, Faculty of Chemistry, University of Warsaw, 02-093 Warsaw, Poland
2Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland

Received 15 December 2014; Revised 22 February 2015; Accepted 1 March 2015

Academic Editor: Mihaly Mezei

Copyright © 2015 Filip Leonarski et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A molecular dynamics simulations of the thymidylate synthase denaturation in chaotrope solvents (urea, guanidinium hydrochloride) were performed on 600 ns timescale. It appeared that this dimeric enzyme undergoes partial unfolding asymmetrically. It was shown also that urea is a better denaturant in the MD condition, as compared to guanidinium chloride. The unfolding occurs first at the external helices (AA 88-118) and follows by the AA 188-200 region. The present results correspond to the suggested in the literature activity of thymidylate synthase through a half-the-site mechanism.