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U‐shaped caveolin‐1 conformations are tightly regulated by hydrogen bonds with lipids
Author(s) -
Park Soohyung,
Glover Kerney J.,
Im Wonpil
Publication year - 2019
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.25807
Subject(s) - hydrogen bond , molecular dynamics , chemistry , helix (gastropod) , crystallography , bilayer , lipid bilayer , umbrella sampling , molecule , membrane , computational chemistry , biochemistry , biology , ecology , organic chemistry , snail
The structure and dynamics of a truncated (residues 82–136) caveolin‐1 (Cav1) construct having a helix‐break‐helix motif are explored by both all‐atom free energy and molecular dynamics (MD) simulations in an explicit bilayer membrane. Two stable Cav1 conformations with small (LB‐Cav1) and large hinge angles (RB‐Cav1) between two helices are identified although their relative free energy cannot be reliably estimated due to the sampling issues. RB‐Cav1s contain one or two lipids residing between the helices that are hydrogen bonded (h‐bonded) to both helices in a multidentate fashion. LB‐Cav1s show the helices with mono‐dentate lipid h‐bond interactions or multidentate interactions limited to a single helix at most. The two conformational states of Cav1 remain their initial state during 2‐μs MD simulation, suggesting that there is a significant hidden barrier (other than the insertion depth of Cav1 and its hinge angle) and the Cav1 conformational states are tightly regulated by the h‐bonds between Cav1 and lipids along with the associated lipid rearrangement during the course of Cav1 conformational changes. © 2019 Wiley Periodicals, Inc.