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Evaluating kinase mechanisms and related proteins

Grant number: 16/08753-6
Support type:Scholarships in Brazil - Master
Effective date (Start): August 01, 2016
Effective date (End): April 30, 2018
Field of knowledge:Physical Sciences and Mathematics - Physics
Principal Investigator:Leandro Cristante de Oliveira
Grantee:Raphael Vinicius Rodrigues Dias
Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Kinases are essential proteins in several biological process as cell control, regulation and signaling transduction. Their regulatory mechanisms can be related to various factors, like chemical environmental variations and/or conformational changes, including the recruitment of adapter proteins. These assumptions emphasise the importance of an detailed understanding of controlling mechanisms involving kinases as well as their function associated with adapter proteins. This proposal aims to evaluate C-terminal Src Kinase (Csk) conformational changes, a protein involved in several regulatory processes such as cell cycling control, neurological development and it is associated to lymphomas or cancers. Also, it will be evaluated the role of electrostatic interactions between the Growth Factor Receptor-Binding Protein (Grb2) and the ligands Coumarin and Morin. The lack of an exploratory molecular interpretation of the functions associated to Csk and Grb2 mechanisms highlights the importance of these investigations. Thus, the identification of target regions may reveal possibilities for future studies involving improvements in medical treatments, i.e., working as a starting point for protein engineering or drugs rational design. The simulations of Grb2 and Csk will be carried out through Molecular Dynamics employing minimalistic models with low computational demand. The interactions between the Grb2 and the suggested ligands will be performed using Molecular Docking. The UCSF Dock and UCSF Chimera packages are the main choice due versatility of force-fields, rescoring function and due the possibility of implementation statistical approaches for more accurate results.