title: Prediction of the structures of helical membrane proteins based on a minimum unfavorable contacts approach.
abstract: An understanding of structure-function relationships of membrane proteins continues to be a challenging problem, owing to the difficulty in obtaining their structures experimentally. This study suggests a method for modeling membrane protein structures that can be used to generate a reliable initial conformation prior to the use of other approaches for sampling conformations. It involves optimizing the orientation of hydrophilic residues so as to minimize unfavorable contacts with the hydrophobic tails of the lipid bilayer. Starting with the optimized initial conformation for three different proteins modeled based on this method, two independent approaches have been used for sampling the conformational space of the proteins. Both approaches are able to predict structures reasonably close to experimental structures, indicating that the initial structure enables the sampling of conformations that are close to the native structure. Possible improvements in the method for making it broadly applicable to helical membrane proteins are discussed.
authors.affiliation: Centre for Computational Natural Sciences and Bioinformatics, International Institute of Information Technology, Hyderabad, 500032, India.
authors.forename: Siladitya
authors.initials: S
authors.lastname: Padhi
authors.forename: Siddabattula
authors.initials: S
authors.lastname: Ramakrishna
authors.forename: U Deva
authors.initials: UD
authors.lastname: Priyakumar
mesh_terms: D003198:Computer Simulation; D008565:Membrane Proteins / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D012984:Software
chemical_list: D008565:Membrane Proteins
keywords: conformational sampling; helical assemblies; ion channels; membrane proteins; protein structure modeling; replica exchange molecular dynamics; structure prediction