BRIGE: Predicting Allosteric Regulation Pathways from Local Elastic Moduli Calculations

This Broadening Participation Research Initiation Grants in Engineering (BRIGE) grant aims at obtaining information on the mechanisms and pathways of allostery on proteins by measuring and analyzing a protein?s 3D map of local mechanical strength. Allostery involves the propagation of signals between sites in a protein structure. A change in function could be brought about by the binding of a ligand, covalent modification or mutation at a distant site. The mechanism of this site-to-site communication is not understood, and is of great interest, especially since allosteric effects must be considered in drug design and protein engineering. The first part of the project will involve development of a technique to calculate the local elastic moduli as a function of the position in space for a molecule, while the second part will focus on applying the resulting 3D maps of local material strength to understand the mechanisms of allostery, find the positions of possible allosteric sites and predict pathways of propagation of allosteric signals through a molecule.

The results will benefit society by improving our understanding of allostery and its connection to many regulatory processes that happen in the human body, and by providing an innovative tool with the potential to revolutionize the field of drug discovery for the treatment of several conditions and diseases, including certain types of cancer. In addition, undergraduate students, and high school students and teachers from underrepresented groups in Puerto Rico and the New York City area will be exposed to the concepts and method through summer internships and visits to the group?s laboratory, with the purpose of broadening the participation of students from these groups and increasing their enrollment into undergraduate and graduate Science, Technology, Engineering and Mathematics (STEM) programs.