From Molecular Dynamics to Genomic Biology: Constructing Kinetic Network Models to Elucidate Transcriptional Fidelity of RNA Polymerase II
A/Prof. Xu-Hui Huang
Hong Kong University of Scientific and Technology

Transcription, the synthesis of RNA from a complementary DNA template, plays a crucial role in cellular regulation, including differentiation, development, and other fundamental processes. In this talk, I will discuss our results on modeling the RNA polymerase II (Pol II, a system with ~400K atoms) Translocation and other functional conformational changes of this enzyme at sub-millisecond timescales. We have developed a novel algorithm, Hierarchical Nystrom Extension Graph method, to construct kinetic network models to extract long timescale dynamics from short simulations. For example, we reveal that RNA polymerase II translocation is driven purely by thermal energy and does not require the input of any additional chemical energy. Our model shows an important role for the bridge helix: Large thermal oscillations of this structural element facilitate the translocation by specific interactions that lower the free-energy barriers between four metastable states. The dynamic view of translocation presented in our study represents a substantial advance over the current understanding based on the static snapshots provided by X-ray structures of transcribing complexes. At the end of my talk, I will briefly discuss our recent progress on extending our kinetic network model to include sequence-dependent molecular dynamics of Pol II elongation to predict transcriptional accuracy in the genome-wide transcriptomic datasets. This model creates a critical link between the structural-mechanics understanding of Pol II fidelity and the genome-wide transcriptional accuracy.

About the Speaker

Prof. Xu-Hui Huang is an Associate Professor of Chemistry and Biomedical Engineering at the Hong Kong University of Scientific and Technology. He obtained his Ph.D. degree from Columbia University in 2006 with Prof. Bruce Berne. He did his postdoc research at Stanford University with Profs. Michael Levitt (Nobel Laureate in Chemistry) and Vijay Pande, He joined HKUST at an assistant professor in 2010, and received an early promotion to the tenured Associated Professor at Jan 2015. His research is focused on developing and applying statistical mechanics based algorithms to model functional conformational changes of complex biological systems. He has published over 70 papers in top journals including Science, Nature, PNAS, and JACS.  Prof. Huang has also received a series of awards including the American Chemical Society Open-Eye Outstanding Junior Faculty Award (2014); School Research Award, HKUST School of Science (2013), and Hong Kong Research Grant Council Early Career Award (2013); and American Chemical Society CCG Excellence Award (2006).

2016-07-12 10:00 AM
Room: A203 Meeting Room
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