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Current Protein & Peptide Science

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ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

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General Research Article

Investigating the Mechanical Properties and Flexibility of N-BAR Domains in PICK1 by Molecular Dynamics Simulations

Author(s): Shenghan Song, Tongtong Li, Amy O. Stevens, Taha Raad and Yi He*

Volume 24, Issue 10, 2023

Published on: 26 September, 2023

Page: [865 - 877] Pages: 13

DOI: 10.2174/1389203724666230522093842

Price: $65

Abstract

Introduction: The proteins of the Bin/Amphiphysin/Rvs167 (BAR) domain superfamily are believed to induce membrane curvature. PICK1 is a distinctive protein that consists of both a BAR and a PDZ domain, and it has been associated with numerous diseases. It is known to facilitate membrane curvature during receptor-mediated endocytosis. In addition to understanding how the BAR domain facilitates membrane curvature, it's particularly interesting to unravel the hidden links between the structural and mechanical properties of the PICK1 BAR domain.

Methods: This paper employs steered molecular dynamics (SMD) to investigate the mechanical properties associated with structural changes in the PICK1 BAR domains.

Results: Our findings suggest that not only do helix kinks assist in generating curvature of BAR domains, but they may also provide the additional flexibility required to initiate the binding between BAR domains and the membrane.

Conclusion: We have observed a complex interaction network within the BAR monomer and at the binding interface of the two BAR monomers. This network is crucial for maintaining the mechanical properties of the BAR dimer. Owing to this interaction network, the PICK1 BAR dimer exhibits different responses to external forces applied in opposite directions.

Keywords: MD simulation, N-BAR domain, mechanical properties, helix kink, curvature key residues, PICK1 protein.

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