CAREER: Computational Modeling of Biological Nanomachines - Protein Unfolding and Translocation by Clp ATPases

University Of Cincinnati Main Campus, Cincinnati OH

Investigators

Abstract

Protein degradation and disassembly of aggregates are critical quality control mechanisms for the maintenance of vital cellular functions. Powerful ring-shaped components of Clp macromolecular machines mediate these actions by using a protein threading mechanism, which consists of recognition, unfolding, and translocation of substrates through a central channel. Understanding the mechanism of these biological nanomachines, that carry out crucial cellular functions, represents an important challenge for modern biological studies. The objective of this CAREER project is to elucidate, using computer simulations, kinetic and thermodynamic requirements for protein unfolding and the operational principles of substrate translocation by the Clp nanomachines. These studies will pinpoint the effect of periodic forces on substrate protein unfolding and translocation and the details of interactions between substrates and Clp responsible for these actions. This project will advance understanding of other protein degradation machines and fundamental principles that govern protein unfolding and translocation. This CAREER project combines interdisciplinary research in computational biophysical chemistry with education and training of undergraduate and graduate students in this field. The educational infrastructure at the University of Cincinnati will be enhanced by establishing a computational biophysical chemistry course taught using problem-based learning and active student participation approaches. The PI will collaborate with Central State University and Fisk University to increase the participation of underrepresented minorities in computational sciences. The scope of these collaborations is to enhance the physical chemistry curriculum and to introduce molecular modeling courses at these universities. The PI will provide research experience opportunities for students at these universities.