Date of Award

Spring 2005

Document Type

Thesis

Degree Name

Master of Science in Computational Biology - (M.S.)

Department

Computer Science

First Advisor

Qun Ma

Second Advisor

Frank Y. Shih

Third Advisor

Alexandros V. Gerbessiotis

Abstract

Soluble guanylyl cyclase (sGC) is one of the key enzymes involved in many fundamental biological processes including vasodilatation. It can be allosterically activated by synthetic compound such as YC-l. Recently, the 3D structure of adenylyl cyclase (AC), which is a homologue of sGC, was determined. Using AC as template and homology modeling, the 3D structure of sGC is predicted. Prior experimental work has suggested two binding modes of YC- 1. In the current investigation, molecular dynamics simulations (MD) were conducted to seek more detail of molecular mechanism of sGC activation.

From these MD simulations, a tentative mechanism of sGC activation is established. The difference in the initial binding modes of YC-l in its binding pocket results in different conformational changes in the active site of sGC, which results in different catalytic capability. Meanwhile, YC-l was found to be strongly attracted to α1 CYS594, a residue deep inside of the allosteric binding pocket.

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