Evolución de la Entropía Durante la Transición Conformacional del Lazo 36 de la Hemaglutinina

Abstract

The transition between the non-fusogenic and fusogenic conformations of loop 36 of the HA2 chain of Hemagglutinin has been studied using the trajectories of molecular dynamics simulations of the loop obtained in a previous work. The original analysis of the data was thouroughly revisited and diferent analytical techniques were used for its analysis. First, the clustering method was evaluated using the Euclidean distance between structures in Ramachandran space, instead of the RMSD, finding evidence of existence of additional intermediate conformations. Importantly, the so called quasi-harmonic approximation was used to estimate entropy. The values of entropy obtained, are in the order of 17 kcal/mol K, which are one order of magnitude higher than the results obtained in previous works. The free energy was estimated based on this improved calculation of the entropy, proving that the term -TS contributes in a non-negligible way to the free energy. The internal energy term was estimated using an ensemble average over the equilibration MD trajectories of each intermediate conformation, as a result the height of the energy barrier for the transition was estimated in 189.75 kcal/mol.