Elucidating protein dynamics and protein-protein interactions using computer modeling and simulations

Abstract

Biological molecules are complex molecules typically consisting of a few thousand atoms. These molecules interact and undergo conformational change to perform biological function. This thesis includes three projects that use computer modelling and simulations, with the aim of predicting protein interactions, mechanism, and properties. To predict the interaction of Transcription Factor IIB C-terminal domain (TFIIBc) and SSU72, we employ a combination of molecular dynamics simulation with protein-protein docking. We have narrowed down the possibilities to three models, ready for validation by experiment. This interaction will be important for the understanding of gene-looping mechanism. The study of clamp domain motion of bacterial RNA Polymerase aims to predict the mechanism of transition from closed clamp to open clamp. Using all-atom MD (aaMD) simulation and coarse-grained MD simulations, we have found some insights on the reaction coordinate and the importance of some regions on RNA Polymerase. Lastly, using aaMD simulation, we have shown the difference in flexibility in the junction region of IQ5 and SAH of Myo7A.

Date of Award	2017
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology