title: Molecular dynamics simulation strategies for protein-micelle complexes.
abstract: The structure and stability of membrane proteins can vary widely in different detergents and this variability has great practical consequences for working with membrane proteins. Nevertheless, the mechanisms that operate to alter the behavior of proteins in micelles are poorly understood and not predictable. Atomic simulations could provide considerable insight into these mechanisms. Building protein-micelle complexes for simulation is fraught with uncertainty, however, in part because it is often unknown how many detergent molecules are present in the complex. Here, we describe several convenient ways to employ Micelle Builder in CHARMM-GUI to rapidly construct protein-micelle complexes and performed simulations of the isolated voltage-sensor domain of voltage-dependent potassium-selective channel and an antimicrobial peptide papiliocin with varying numbers of detergents. We found that once the detergent number exceeds a threshold, protein-detergent interactions change very little and remain very consistent with experimental observations. Our results provide a platform for future studies of the interplays between protein structure and detergent properties at the atomic level. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.
authors.affiliation: Department of Molecular Biosciences and Center for Computational Biology, The University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea.
authors.forename: Jin-Kyoung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Korea.
authors.forename: Yangmee
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Chemistry and Biochemistry, UCLA, 611 Charles E. Young Dr. E, Los Angeles, CA 90095-1570, USA.
authors.forename: James U
authors.initials: JU
authors.lastname: Bowie
authors.affiliation: Department of Molecular Biosciences and Center for Computational Biology, The University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, USA. Electronic address: wonpil@ku.edu.
authors.forename: Wonpil
authors.initials: W
authors.lastname: Im
mesh_terms: D040761:Biomimetic Materials / Q000737:chemistry; D003902:Detergents / Q000737:chemistry*; D008563:Membrane Lipids / Q000737:chemistry*; D008565:Membrane Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D008823:Micelles; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D012984:Software; D013329:Structure-Activity Relationship
chemical_list: D003902:Detergents; D008563:Membrane Lipids; D008565:Membrane Proteins; D008823:Micelles
keywords: Papiliocin; Protein–detergent interactions; Voltage-dependent potassium-selective channel