title: Simulations of fatty acid-binding proteins. II. Sites for discrimination of monounsaturated ligands.
abstract: Fatty acid binding proteins (FABPs) can discriminate between saturated and unsaturated fatty acids via molecular mechanisms that are not understood. Molecular dynamics computer calculations are used to suggest the relationship between tertiary structure and binding specificity. Three separate 1-ns simulations, with explicit solvent, are presented: 1) oleic acid (C18:1 cis) bound to adipocyte FABP, 2) oleic acid bound to human muscle FABP, and 3) elaidic acid (C18:1 trans) bound to human muscle FABP. The average structural, dynamic, and energetic properties of the trajectory were analyzed, as were the motional correlations. The molecular dynamics trajectories reveal intriguing differences among all three systems. For example, the two proteins have different strengths of interaction energy with the ligand and different motional coupling, as seen with covariance analysis. This suggests distinctive molecular behavior of monounsaturated fatty acids in the two similar proteins. An importance scale, based on motional correlation and interaction energy between protein and ligand, is proposed, to help identify amino acids involved with the discrimination of ligand saturation state or geometric isomerization.
authors.affiliation: Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. twoolf@welchlink.welch.jhu.edu
authors.forename: T B
authors.initials: TB
authors.lastname: Woolf
authors.forename: M
authors.initials: M
authors.lastname: Tychko
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D018482:Muscle, Skeletal / Q000378:metabolism; D018996:Myelin P2 Protein / Q000737:chemistry* / Q000378:metabolism*; D009363:Neoplasm Proteins; D019301:Oleic Acid / Q000737:chemistry / Q000378:metabolism*; D009829:Oleic Acids; D017434:Protein Structure, Tertiary; D012984:Software; D012997:Solvents; D025521:Tumor Suppressor Proteins; D014867:Water
chemical_list: D002352:Carrier Proteins; C493404:FABP2 protein, human; C107608:FABP7 protein, human; C493405:Fabp2 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009829:Oleic Acids; D012997:Solvents; D025521:Tumor Suppressor Proteins; D014867:Water; D019301:Oleic Acid; C011459:elaidic acid