Topics in Protein Folding and Dynamics

马里兰州大学帕克分校的Devarajan Thirumalai由理论和计算化学计划资助，并由分子和细胞生物科学部的分子生物物理计划共同资助，以建立在他之前NSF支持的工作基础上。他的研究为理解受限体积中的折叠、RNA折叠和伴侣蛋白介导的折叠提供了概念框架。研究小组将重点放在三个方面。(1)在第一个领域，正在探索使用模型系统和肽和分子动力学来破译变性剂的解折叠作用。(2)在第二个项目中，该团队正在评估纳米孔和拥挤的限制效应，同时使用最小的非晶格模型进行计算，探索蛋白质折叠的热力学和动力学。(3)最后，PI使用基质蛋白质的非晶格模型和GroEL腔的粗粒度描述来解决GroEL纳米机器如何帮助折叠大量结构无关蛋白质的问题。这项工作预计将产生广泛的影响，有助于破译管理生物分子功能的一般原则。

Devarajan Thirumalai of University of Maryland, College Park is funded by the Theoretical and Computational Chemistry program and co-funded by the Molecular Biophysics program of the Division of Molecular and Cellular Biosciences to build on on his prior NSF-supported work. His research provides conceptual frameworks for understanding folding in confined volumes, RNA folding, and chaperonin-mediated folding. The research team is focusing their efforts in three areas. (1) In the first area, the use of model systems and peptides and molecular dynamics to decipher the unfolding action of denaturants is being explored. (2) In the second project, the team is assessing the effects of confinement in nanopores and crowding, while carrying out calculations that probe the thermodynamics and kinetics of protein folding using minimal off-lattice models. (3) Finally, using off-lattice models for the substrate proteins and a coarse-grained description for the GroEL cavity the PI is addressing the question of how the GroEL nanomachine aids in the folding of a large number of structurally unrelated proteins. The work is expected to have a broad impact by contributing to the deciphering of general principles that govern the function of biomolecules.