Sensitivity of Coarse Grain Models of Peptides to the Introduction of Charged Residues in Model Peptides and Bacterial Chemoreceptors

Abstract

Coarse grain (CG) techniques for molecular simulation have become increasingly popular over recent years, and have been shown to offer useful insights into a variety of different systems including protein conformational change, protein-membrane interaction and protein-protein interaction. Recently, the appropriateness of MARTINI based CG models for modelling introduction of arginine residues into the membrane has been called into question by explicit PMF calculations. We have used high throughput simulation techniques to probe the appropriateness of simulating arginine residues within the membrane core in the novel model peptide GWALP23 (GGALW(LA)6LWLAGA), alongside experimental evidence from solid state NMR techniques. We find close agreement between experimental and simulation results for two modifications of GWALP; introduction of arginine at position 14, which creates a stable TM helix with increased tilt and introduction of arginine at position 12, which creates an helix which adopts multiple positions (TM and interfacial). These results allow for the interpretation of mutational data from genetic screens of the bacterial chemoreceptor. In particular, the role of helix rotation in chemoreceptor signalling processes is clarified and the wild type behaviour understood.