Binding free energy calculations for computational measurements of enthalpy and entropy in protein-ligand interactions

• Grant number: 15/01709-9
• Support type: Scholarships abroad - Research Internship - Master's degree
• Effective date (Start): July 01, 2015
• Effective date (End): October 31, 2015
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal researcher: Alessandro Silva Nascimento
• Grantee: João Victor de Souza Cunha
• Supervisor abroad: Michael K. Gilson
• Home Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil
• Research place: University of California, San Diego (UC San Diego), United States
• Associated to the scholarship: 14/01751-2 - Monte Carlo applications in a docking algorithim for creation of new ensembles and free energy calculation, BP.MS

Abstract

The non-covalent interactions in protein-ligand binding are key factors for most biomolecular phenomena such as molecular recognition, cellular communication and enzymatic activity. Therefore, a deeper understanding of molecular recognition at a molecular level and by quantitative means is crucial. Among the quantities involved in the recognition process, the interaction free energy as well as its enthalpic and entropic components stand out in terms of relevance but also in difficulty to estimate. In this project, our goal is to use the software under development in our group to estimate the free energy of binding, together with the enthalpy and the entropy changes, using statistical thermodynamics and Monte-Carlo simulations. We expect to deeper the current understanding on biomolecular binding and to deliver a computational tool useful in the design of new drugs design reaching a diverse range of biotechnology applications. (AU)