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Title: Different dynamics and pathway of disulfide bonds reduction of two human defensins, a molecular dynamics simulation study: Different Dynamics and Pathway of Disulfide Bonds Reduction

Abstract

Human defensins are a class of antimicrobial peptides that are crucial components of the innate immune system. Both human α defensin type 5 (HD5) and human β defensin type 3 (hBD‐3) have 6 cysteine residues which form 3 pairs of disulfide bonds in oxidizing condition. Disulfide bond linking is important to the protein structure stabilization, and the disulfide bond linking and breaking order have been shown to influence protein function. In this project, microsecond long molecular dynamics simulations were performed to study the structure and dynamics of HD5 and hBD‐3 wildtype and analogs which have all 3 disulfide bonds released in reducing condition. The structure of hBD‐3 was found to be more dynamic and flexible than HD5, based on RMSD, RMSF, and radius of gyration calculations. The disulfide bridge breaking order of HD5 and hBD‐3 in reducing condition was predicted by two kinds of methods, which gave consistent results. It was found that the disulfide bonds breaking pathways for HD5 and hBD‐3 are very different. The breaking of disulfide bonds can influence the dimer interface by making the dimer structure less stable for both kinds of defensin. In order to understand the difference in dynamics and disulfide bond breaking pathway,more » hydrophilic and hydrophobic accessible surface areas (ASA), buried surface area between cysteine pairs, entropy of cysteine pairs, and internal energy were calculated. Comparing to the wildtype, hBD‐3 analog is more hydrophobic, while HD5 is more hydrophilic. For hBD‐3, the disulfide breaking is mainly entropy driven, while other factors such as the solvation effects may take the major role in controlling HD5 disulfide breaking pathway. Proteins 2017; 85:665–681. © 2016 Wiley Periodicals, Inc.« less

Authors:
ORCiD logo [1]
  1. Department of Chemical Engineering, Tennessee Technological University, Cookeville TN 38505
Publication Date:
Research Org.:
Oak Ridge National Laboratory, Oak Ridge Leadership Computing Facility (OLCF)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1565542
Resource Type:
Journal Article
Journal Name:
Proteins
Additional Journal Information:
Journal Volume: 85; Journal Issue: 4; Journal ID: ISSN 0887-3585
Publisher:
Wiley
Country of Publication:
United States
Language:
English
Subject:
Biochemistry & Molecular Biology; Biophysics

Citation Formats

Zhang, Liqun. Different dynamics and pathway of disulfide bonds reduction of two human defensins, a molecular dynamics simulation study: Different Dynamics and Pathway of Disulfide Bonds Reduction. United States: N. p., 2017. Web. doi:10.1002/prot.25247.
Zhang, Liqun. Different dynamics and pathway of disulfide bonds reduction of two human defensins, a molecular dynamics simulation study: Different Dynamics and Pathway of Disulfide Bonds Reduction. United States. doi:10.1002/prot.25247.
Zhang, Liqun. Tue . "Different dynamics and pathway of disulfide bonds reduction of two human defensins, a molecular dynamics simulation study: Different Dynamics and Pathway of Disulfide Bonds Reduction". United States. doi:10.1002/prot.25247.
@article{osti_1565542,
title = {Different dynamics and pathway of disulfide bonds reduction of two human defensins, a molecular dynamics simulation study: Different Dynamics and Pathway of Disulfide Bonds Reduction},
author = {Zhang, Liqun},
abstractNote = {Human defensins are a class of antimicrobial peptides that are crucial components of the innate immune system. Both human α defensin type 5 (HD5) and human β defensin type 3 (hBD‐3) have 6 cysteine residues which form 3 pairs of disulfide bonds in oxidizing condition. Disulfide bond linking is important to the protein structure stabilization, and the disulfide bond linking and breaking order have been shown to influence protein function. In this project, microsecond long molecular dynamics simulations were performed to study the structure and dynamics of HD5 and hBD‐3 wildtype and analogs which have all 3 disulfide bonds released in reducing condition. The structure of hBD‐3 was found to be more dynamic and flexible than HD5, based on RMSD, RMSF, and radius of gyration calculations. The disulfide bridge breaking order of HD5 and hBD‐3 in reducing condition was predicted by two kinds of methods, which gave consistent results. It was found that the disulfide bonds breaking pathways for HD5 and hBD‐3 are very different. The breaking of disulfide bonds can influence the dimer interface by making the dimer structure less stable for both kinds of defensin. In order to understand the difference in dynamics and disulfide bond breaking pathway, hydrophilic and hydrophobic accessible surface areas (ASA), buried surface area between cysteine pairs, entropy of cysteine pairs, and internal energy were calculated. Comparing to the wildtype, hBD‐3 analog is more hydrophobic, while HD5 is more hydrophilic. For hBD‐3, the disulfide breaking is mainly entropy driven, while other factors such as the solvation effects may take the major role in controlling HD5 disulfide breaking pathway. Proteins 2017; 85:665–681. © 2016 Wiley Periodicals, Inc.},
doi = {10.1002/prot.25247},
journal = {Proteins},
issn = {0887-3585},
number = 4,
volume = 85,
place = {United States},
year = {2017},
month = {2}
}

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