Procesos físicos en sistemas biomoleculares : transición conformacional del lazo 36 de la proteína Hemaglutinina.

Abstract

Loop 36 is a polypeptide that is part of the HA2 chain of hemagglutinin, a protein found on the surface of influenza virus. The transition of the polypeptide from its partially random state to its fully folded state was studied by characterizing the change of its free energy as a function of a reaction coordinate, obtaining a potential mean force (PMF). The strategy for calculating the PMF combines a TMD simulation to obtain a first sampling of the conformational space of the polypeptide, cluster analysis to obtain representative structures of the transition and the Umbrella sampling method to obtain complete information of the conformational space of the loop 36. The criteria used to determine the similarity between clusters was to define a sampling resolution associated to the width of a peak of the PMF curve obtained from the TMD simulation. With this protocol, 10 representative structures were obtained and used as sampling windows. Thus, the PMF associated with the natural transition of loop 36 was obtained, here it was found that for the system to reach its fully folded state, it must cross a potential barrier of a height equal to 2.5 [kcal/mol] when the distance between centers of mass of the lower and upper part of the polypeptide is equal to 25.4 [Å] and it was found that the global energy.