Chemistry and Chemical Biology ETDs

Publication Date

Spring 5-11-2024

Abstract

Protein function is closely related to their three-dimensional structures. However, some proteins lack a well-defined structure, so-called intrinsically disordered proteins (IDPs). They prefer to interconvert among different conformations in isolation and undergo a disorder-to-order transition upon binding to a partner. IDPs or proteins with intrinsically disordered regions (IDRs), constituting a large portion of the human proteome, are involved in many cellular activities and are therefore highly relevant to our health. In my dissertation, I used computational methods to systematically study systems including dynamic proteins, disordered proteins in complex with their targets, and synthetic peptidomimetics to reveal the unique physical properties and biological behaviors of IDPs/IDRs and ultimately to provide insights into rationally designing drugs to target protein-protein interactions. Through all-atom/coarse-grained molecular dynamics (MD) simulations, the conformational spaces of IDPs/IDRs/peptidomimetics can be reconstructed and the binding/unbinding pathways of protein complexes can be monitored in detail.

Language

English

Keywords

Disordered proteins, protein-protein interactions, protein binding/unbinding pathways, peptidomimetics, molecular dynamics (MD) simulations, all-atom/coarse-grained force fields

Document Type

Dissertation

Degree Name

Chemistry

Level of Degree

Doctoral

Department Name

Department of Chemistry and Chemical Biology

First Committee Member (Chair)

Dr. Yi He

Second Committee Member

Dr. Jeremy Edwards

Third Committee Member

Dr. Mark Walker

Fourth Committee Member

Dr. Matthew Lakin

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