Large scale docking screening and simulations of molecular dynamics for the study of ligand binding in different protein models

Molecular recognition is central to biology, it is the starting point for almost all processes in biological systems; knowledge of the molecular association aids in understanding a variety of pathways taking place in the living cell. Molecular binding is an attractive interaction between two molecules which results in a stable molecular complex. Among computational applications, docking is the methodology for predicting the complex. There are many docking strategies, fast molecular docking and absolute binding free energies are applied in this work. These methodologies have been applied to three biological systems: neuraminidase of H5N1 influenza virus, human Endothelial Protein C receptor (EPCR) and β-tubulin of the psycrophilic organism, Euplotes focardii. In particular, the first study is a drug design application; two selective ligands for the open conformation of the H5N1 influenza virus neuraminidase has been obtained, performing a comparative binding study with fast molecular docking and specific interaction filters. In the second study structurally stable mutants of EPCR with impaired binding affinity for phosphatidylethanolamine (PTY), will be designed and selected for the analysis of the ligand role in EPCR function. In the third work the structural adaptation to low temperature of the three β-tubulin isotypes are analysed employing molecular dynamics simulations. The applied computational methods allow to obtain accurate predictions in the field of binding analysis. In particular, fast molecular docking allows to obtain the correct binding mode and provide a good approximation of the interaction energy; molecular dynamics supply accurate binding affinities and is a useful tool for the study of the effect of ligand binding on protein structures.