Conformational Heterogeneity and transition states based on Cryo-EM maps and hybrid methods

• Grant number: 24/18588-9
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2028
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Ana Lígia Barbour Scott
• Grantee: Ana Lígia Barbour Scott
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The role of structural dynamics, also called intrinsic dynamics, in the interactions and functioning of biomolecular systems in the cell has attracted considerable interest in recent experimental and computational studies. Macromolecules often transition between the stable conformations amenable to experimental determination and these conformational changes have important functional and regulatory roles. For example, enzymes, channels, transporters, and pumps must alter their shapes and visit many conformational states to perform their functions. Structural dynamics play essential roles in signaling, catalysis, and other fundamental activities in cells. Characterizing the full ensemble of conformations visited by a given macromolecular system is therefore essential to deciphering. Our research hypothesis is that conformational changes, dynamics and transient conformations are critically important for protein function, yet methods to map out pathways and identify transient structures lag behind the methods used for structure determination of well-populated stable states. Use the structural information obtained from combining computational and experimental data in numerical simulations to build Markov state models in order to characterize conformational transition pathways. The research issues and chosen research theme, that being a project at the fundamental level involving key instrumentation cryo-EM tied together by theoretical molecular dynamics simulations, addresses the work challenge theme. The developments anticipated will have the potential of becoming a tool for characterization of structural dynamics of very large biomolecular complexes. (AU)