Evaluating kinase mechanisms and related proteins

• Grant number: 16/08753-6
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2016
• End date: April 30, 2018
• Field of knowledge: Physical Sciences and Mathematics - Physics - Condensed Matter Physics
• Principal Investigator: Leandro Cristante de Oliveira
• Grantee: Raphael Vinicius Rodrigues Dias
• Host 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.

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANCHES, KAROLINE; RODRIGUES DIAS, RAPHAEL VINICIUS; DA SILVA, PAULO HENRIQUE; FOSSEY, MARCELO ANDRES; CARUSO, ICARO PUTINHON; DE SOUZA, FATIMA PEREIRA; DE OLIVEIRA, LEANDRO CRISTANTE; DE MELO, FERNANDO ALVES. Grb2 dimer interacts with Coumarin through SH2 domains: A combined experimental and molecular modeling study. HELIYON, v. 5, n. 11, NOV 2019. (14/17630-0, 09/53989-4, 16/08753-6)

DIAS, RAPHAEL VINICIUS RODRIGUES; FERREIRA, CAROLINA TATIANI ALVES; JENNINGS, PATRICIA ANN; WHITFORD, PAUL CHARLES; DE OLIVEIRA, LEANDRO CRISTANTE. Csk ?C Helix: A Computational Analysis of an Essential Region for Conformational Transitions. Journal of Physical Chemistry B, v. 126, n. 50, p. 10-pg., 2022-12-13. (16/08753-6)

BALDASSA, MONIZE A. B.; DIAS, RAPHAEL V. R.; OLIVEIRA, LEANDRO C.; FEITOSA, ELOI. Aqueous mixtures of cornstarch and Pluronic? F127 studied by experimental and computational techniques. Food Research International, v. 158, p. 9-pg., 2022-06-27. (16/08753-6)

SANCHES, KAROLINE; DIAS, RAPHAEL V. R.; DA SILVA, PAULO H.; CARUSO, ICARO P.; FOSSEY, MARCELO A.; DE SOUZA, FATIMA P.; DE OLIVEIRA, LEANDRO C.; MELO, FERNANDO A.. Thermodynamic profile and molecular modeling of the interaction between Grb2 dimer and flavonoids Rutin and Morin. Journal of Molecular Structure, v. 1234, p. 10-pg., 2021-03-06. (16/08753-6, 14/17630-0, 19/24974-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

DIAS, Raphael Vinicius Rodrigues. Computational evaluation of mechanisms of kinases and related proteins. 2018. Master's Dissertation - Universidade Estadual Paulista (Unesp). Instituto de Biociências Letras e Ciências Exatas. São José do Rio Preto São José do Rio Preto.