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Atomistic simulations of a protein unfolding process at room temperature using the weighted ensemble path sampling strategy

Bellesis, Andrew (2020) Atomistic simulations of a protein unfolding process at room temperature using the weighted ensemble path sampling strategy. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Developing a detailed understanding of protein folding and unfolding processes, including the conformational details of the unfolded state ensemble, has been a longstanding challenge in biophysics. In particular, the transient states of these processes have been difficult to capture using experimental techniques such as NMR spectroscopy and the timescales associated with both processes are beyond the microsecond timescales that can be accessed by standard molecular dynamics (MD) simulations. Here, the weighted ensemble (WE) path sampling strategy was employed in conjunction with MD simulations to enable the simulation of protein unfolding events at room temperature. The WE strategy has enabled the simulation of rare events such as ligand binding, large protein conformational transitions, and protein unfolding. I present atomically detailed simulations of the unfolding process of the G29A mutant of the B-domain of protein A from the virulence factor, Streptococcal aureus (BdpA) at room temperature and characterize the conformational details of representative unfolding pathways.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Bellesis, Andrewagb53@pitt.eduagb530000-0003-2853-0057
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairChong, Lillianltchong@pitt.edultchong0000-0002-0590-483X
Committee MemberKenneth, Jordanjordan@pitt.edujordan0000-0001-9178-6771
Committee MemberAngela, Gronenbornamg100@pitt.eduamg1000000-0001-9072-3525
Committee MemberJacob, Durrantdurrantj@pitt.edudurrantj0000-0002-5808-4097
Date: 8 June 2020
Date Type: Publication
Defense Date: 21 February 2020
Approval Date: 8 June 2020
Submission Date: 6 March 2020
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 31
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Molecular Biophysics and Structural Biology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: molecular modeling, protein folding, molecular dynamics, weighted ensemble, computational chemistry, protein biophysics
Date Deposited: 08 Jun 2020 15:02
Last Modified: 08 Jun 2020 15:02
URI: http://d-scholarship.pitt.edu/id/eprint/38487

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