BRIGE: Predicting Allosteric Regulation Pathways from Local Elastic Moduli Calculations

这个扩大参与研究启动工程（BRIGE）赠款赠款的目的是通过测量和分析蛋白质，获得有关蛋白质变构的机制和途径的信息？局部机械强度的3D图。变构涉及蛋白质结构中位点之间的信号传播。功能的改变可以通过配体的结合、共价修饰或远端位点的突变来实现。这种位点间通讯的机制尚不清楚，但引起了极大的兴趣，特别是因为在药物设计和蛋白质工程中必须考虑变构效应。该项目的第一部分将涉及开发一种技术来计算局部弹性模量作为分子空间位置的函数，而第二部分将专注于应用所产生的局部材料强度的3D地图来理解变构的机制，找到可能的变构位点的位置并预测变构信号通过分子的传播途径。 这些结果将通过提高我们对变构的理解及其与人体内发生的许多调节过程的联系，并通过提供一种创新工具来改变药物发现领域的潜力，从而使社会受益，用于治疗多种疾病和疾病，包括某些类型的癌症。此外，来自波多黎各和纽约市地区代表性不足群体的本科生、高中生和教师将通过暑期实习和访问该群体接触到这些概念和方法？的实验室，扩大这些群体的学生的参与，并增加他们的入学本科和研究生科学，技术，工程和数学（STEM）课程的目的。

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.