Semester

Summer

Date of Graduation

2021

Document Type

Dissertation

Degree Type

PhD

College

Eberly College of Arts and Sciences

Department

Chemistry

Committee Chair

Blake Mertz

Committee Member

Brian Popp

Committee Member

Fabien Goulay

Committee Member

Stephen Valentine

Committee Member

Ucheor Choi

Abstract

Molecular dynamics (MD) simulations have gained impetus as a technique for elucidating structural and dynamical information about membrane proteins (MP). In particular, coarse-grained (CG) MD simulations have provided valuable information about the relationship between membrane components and supramolecular organization of MPs. In this work MD simulations are used to characterize the effects of hopanoids on bacterial membrane dynamics and association in a model protein proteorhodopsin (PR), as well as the role of the extended C-terminus of the human adenosine receptor (A2AR) on its dimerization. PR is found to dimerize in a manner that is dependent on both the type and concentration of hopanoid. High residence times of PR-hopanoid interactions on certain helices result in weakly bound complexes that decrease the participation of those helices at the dimer interface. In the case of the A2AR, the extended C-terminus was found to play a stabilizing role in its dimerization via a network of electrostatic interactions that can be tuned by the C-terminal chain length. Taken together, these results provide a glimpse into potential allosteric modulation of MP dimer interfaces via changing the membrane composition or controlling intrinsic properties of a MP such as its C-terminus for desired pharmacological benefits.

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