Modeling and Simulating Biomolecular Machineries at Atomic Scale and Beyond

Biomolecular machineries are molecular complexes endowed with sophisticated machine-like functions inside living organisms. Understanding how these machineries achieve their functions at the microscopic structural level could be essential for understanding fundamental principles of life as well as for engineering molecular devices for the purpose of technology advancement and medical research. This work describes a computational research investigating three biomolecular systems which are simple and ubiquitous, namely, (1) a DNA helicase PcrA, a prototype molecular motor traveling along DNA, for which we have provided evidence for an alternating domain mobilities mechanism that controls the directional translocation; (2) a membrane channel protein Aquaporin-1 (AQP1), conducting water through its individual monomeric pores, for which we have proposed a feasible mechanism of gating and ion conduction in its tetramerical central pore; (3) a four-way DNA junction (Holliday junction), a central intermediate in homologous recombination, for which we have constructed a minimum geometric model and deduced a schematic framework of its conformer transition. The studies have been conducted mainly by modeling the molecular systems at the atomic scale and simulating them using molecular dynamics (MD) techniques. Since physiological functions of those systems usually involve time scales much longer that can currently achieve through atomic-scale MD simulations, other computational approaches have also been adopted to complement the atomistic descriptions. In particular, the study of PcrA helicase systematically implemented a variety of computational techniques and gives a comprehensive example of how to investigate a biomolecular machine working across multiple time and length scales. All the studies were conducted in close contact with experimental research, and the validity of the studies can be directly tested through experiments.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Physics

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Yu, Jin

Contributors dc:contributor

• Schulten, Klaus

• Biophysics, General

Language dc:language

eng

Identifier

(MiAaPQ)AAI3290448

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/80558