Structural studies of microtubule polymerization dynamics and its modulation by the action of anticancer drugs

• Grant number: 13/11950-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: September 01, 2013
• End date: August 31, 2014
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Adriano Defini Andricopulo
• Grantee: Ricardo Nascimento dos Santos
• Supervisor: José Nelson Onuchic
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Institution abroad: Rice University, United States
• Associated to the scholarship: 10/06741-4 - Structure- and ligand based-drug design of new chemotherapeutic agents for the treatment of cancer, BP.DD

Abstract

Cancer is the name of a group of devastating diseases characterized by uncontrolled growth and multiplication of abnormal cells capable of invading nearby structures and spread in various regions of the body. These malignant cells fail to respond to control and defense mechanisms of the body, continually doubling in a disorderly manner and causing tumors. The world scenario caused by devastating cancer can be estimated taking into account the number of 7.6 million deaths in 2008, representing 13% of total deaths worldwide. It is estimated that the number of new cancer cases in the United States in 2013 is nearly 1.7 million. In Brazil, this disease is the second leading cause of death, demonstrating the extreme importance of developing new drugs more efficient for the treatment of cancer. Due to its essential role in mitosis, microtubules represent an interesting target for the development of anticancer drugs. This project proposes a scientific collaboration between the Laboratório de Química Medicinal e Computacional (LQMC) from University of São Paulo (USP) and the Center for Theoretical Biological Physics (CTBP) from Biosciences Research Collaborative department at Rice University to develop research studies focused on the elucidation of the molecular mechanisms related to microtubule polymerization and to its modulation in the presence of anticancer drugs. These studies will greatly contribute to the scientific background of the student by the introduction of modern computational techniques well established by CTBP, like structure-based model (SBM) and direct-coupling analysis (DCA), and also to the development of new microtubule modulators with improved potency and drug-like properties from the compounds already identified in LQMC. (AU)

Scientific publications

(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)

DOS SANTOS, RICARDO N.; MORCOS, FARUCK; JANA, BIMAN; ANDRICOPULO, ADRIANO D.; ONUCHIC, JOSE N.. Dimeric interactions and complex formation using direct coevolutionary couplings. SCIENTIFIC REPORTS, v. 5, SEP 4 2015. (13/11950-0)