Coarse-grained modeling with constant pH of the protein complexation phenomena

• Autor(a) principal: Cuevas, Sergio Alejandro Poveda
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Biblioteca Digital de Teses e Dissertações da USP
• Texto Completo: http://www.teses.usp.br/teses/disponiveis/95/95131/tde-09062017-123617/
• topic: Coarse-grained model; Complexação de proteína; Computer simulation; Modelagem molecular; Modelo de granulidade grossa; Molecular modeling; Monte Carlo; Monte Carlo; Protein complexation; Second virial coefficient B2; Segundo coeficiente de virial B2; Simulação computacional

Theoretical studies of the molecular mechanisms responsible for the formation and stability of protein complexes have gained importance due to their practical applications in the understanding of the molecular basis of several diseases, in protein engineering and biotechnology. The objective of this project is to critically analyze and refine a coarse-grained force field for protein-protein interactions based on experimental thermodynamic properties and to apply it to cancer-related S100A4 protein system. Our ultimate goal is to generate knowledge for a better understanding of the physical mechanisms responsible for the association of particular proteins in different environments. We studied the role of short and long-range interactions on the complexation of homo-associations. Furthermore, we analyzed the influence of the pH and its correlation with the charge regulation mechanism. We analyzed and refined the adjustable Lennard-Jones parameter for a mesoscopic model based on experimental second virial data for lysozyme, chymotrypsinogen, and ribonuclease A via Monte Carlo simulations. From of that, the S100A3 protein was used to test the new calibrated parameters. Finally, we evaluated the dimerization process of S100A4 proteins, observing the role of physical-chemistry variables involved in the thermodynamical stability of different oligomers.