title: How reliable are molecular dynamics simulations of membrane active antimicrobial peptides?
abstract: Membrane-active antimicrobial peptides (AMPs) are challenging to study experimentally, but relatively easy to investigate using molecular dynamics (MD) computer simulations. For this reason, a large number of MD studies of AMPs have been reported over recent years. Yet relatively little effort has focused on the validity of such simulations. Are these results reliable, and do they agree with what is known experimentally? And how much meaningful information can be obtained? To answer these questions, we demonstrate here some of the requirements and limitations of running MD simulations for several common AMPs: PGLa, melittin, maculatin and BP100. The two most important findings are: (a) simulation results depend strongly on force field parameters, making experimental verification of the simulations obligatory, and (b) slow orientational and conformational fluctuations mean that much longer sampling timescales (multi-μs) are needed if quantitative agreement between simulation averages and experimental data is to be achieved. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.
authors.affiliation: The State Key Laboratory of Microbial Metabolism and College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Microbial Metabolism and College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Tangzheng
authors.initials: T
authors.lastname: Zhao
authors.affiliation: The State Key Laboratory of Microbial Metabolism and College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: dqwei@sjtu.edu.cn.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Wei
authors.affiliation: Institute of Biological Interfaces (IBG-2), Karlsruhe Institute of Technology, P.O.B. 3640, 76021 Karlsruhe, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Strandberg
authors.affiliation: Institute of Biological Interfaces (IBG-2), Karlsruhe Institute of Technology, P.O.B. 3640, 76021 Karlsruhe, Germany; Institute of Organic Chemistry, Karlsruhe Institute of Technology, Fritz-Haber Weg 6, 76131 Karlsruhe, Germany.
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
authors.affiliation: Department of Physics, Shanghai Jiao Tong University, Shanghai 200240, China; The Institute of Natural Sciences, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: jakob@sjtu.edu.cn.
authors.forename: Jakob P
authors.initials: JP
authors.lastname: Ulmschneider
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry; D003198:Computer Simulation; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008555:Melitten / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D009842:Oligopeptides / Q000737:chemistry*; D011498:Protein Precursors / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D009842:Oligopeptides; C088254:PGLa prepropeptide; D011498:Protein Precursors; C540525:lysyl-lysyl-leucyl-phenylalanyl-lysyl-lysyl-isoleucyl-leucyl-lysyl-tyrosyl-leucinamide; D008555:Melitten
keywords: Antimicrobial peptide PGLa; BP100; Lipid bilayer membrane; MD force field; Maculatin; Melittin