University of Illinois at Chicago
WU-DISSERTATION-2022.pdf (9.64 MB)

Energy Flow Perspective on the Mechanism of the Conformational Dynamics in Biomolecules

Download (9.64 MB)
posted on 2022-12-01, 00:00 authored by Shanshan Wu
Most functional processes of proteins involve significant conformational changes. In those activated processes, the system needs to cross an energy barrier. A comprehensive understanding of activated dynamics is necessary for understanding protein functions. We developed a rigorous method for computing the potential and kinetic energy flows of individual coordinates, which define the energy cost of their movements. Moreover, by introducing the generalized work functional, a fundamental mechanical operator that can characterize the effects of mechanical coupling, we can identify the reaction coordinates that determine the progress of a reaction process. Applying these methods to the isomerization reaction of an alanine dipeptide, we found that a large amount of kinetic energy accumulates in the reaction coordinates before the system starts to cross the activation barrier, which is then used to cover the potential energy cost during barrier crossing. Additionally, we studied the flap opening process of HIV-1 protease, which is essential for substrate binding. Through the energy flow analysis of individual coordinates, we found the extent of energy accumulations strongly correlates with the scale of movements of residues. The coordinates precisely cooperate to form collective modes with high-energy flows and control the reaction dynamics. Our method provides a rigorous scheme to systematically study the contributions of different coordinates to the reactive process and extract the coordinate collectivity from the energy flow perspective, which is fundamentally different from the intuition-guided approaches.



Ma, Ao


Ma, Ao


Biomedical Engineering

Degree Grantor

University of Illinois at Chicago

Degree Level

  • Doctoral

Degree name

PhD, Doctor of Philosophy

Committee Member

Liang, Jie Dai, Yang Peng, Zhangli Khalili-Araghi, Fatemeh

Submitted date

December 2022

Thesis type



  • en

Usage metrics


    No categories selected


    Ref. manager