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Access Type

WSU Access

Date of Award

1-1-2010

Degree Type

Thesis

Degree Name

M.S.

Department

Biomedical Engineering

First Advisor

Yeshitila Gebremichael

Abstract

Structural studies devoted to m- and µ- calpains have proposed a two stage calcium dependent activation mechanism for calpains. In this work, we performed molecular dynamics simulations to investigate the global and the local changes in the structure of f the protease core upon calcium binding. Simulations were performed on the protease core of calcium free m- calpain and the protease core of calcium bound m- calpain with and without calcium ions. Our results indicated that the inactive, open conformation of the protease core may not transform into the active, closed conformation simply upon removal of constraints from the outside domains. We also propose that when the indole ring of W288 is oriented away from in between the sub domains IIa and IIb, the protease core tends to adopt a closed conformation and when it is oriented in between the two sub domains, the protease core tends to adopt an open conformation.

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