title: Simulations of fatty acid-binding proteins suggest sites important for function. I. Stearic acid.
abstract: Molecular dynamics simulations of two structurally similar fatty acid-binding proteins interacting with stearic acid are described. The calculations relate to recent ligand binding measurements and suggest similarities and differences between the two systems. Charged and neutral forms of the fatty acid were examined. The charged forms led to rapid trajectory divergence, whereas the protonated forms remained stable over the length of their 1-ns production trajectories. The two protein systems showed similar sets of total interaction energies with the ligand. However, the strengths of individual amino acids interacting with the ligand differ. Furthermore, covariance analysis of the ligand with both protein and water suggests that the stearic acid in the adipocyte fatty acid-binding protein is coupled more strongly to the water than to the protein. The stearic acid in the muscle fatty acid-binding protein is seen to be coupled differentially along the length of the chain to the protein. These differences could help to rationalize the stronger binding affinity for stearic acid in the human muscle fatty acid-binding protein. An importance scale, based on both covariance and interaction energy with the ligand, is proposed to identify residues that may be important for binding function.
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
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D003196:Computer Graphics; D018360:Crystallography, X-Ray; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D006801:Humans; D006860:Hydrogen Bonding; D008954:Models, Biological; D008958:Models, Molecular; D018482:Muscle, Skeletal / Q000378:metabolism; D018996:Myelin P2 Protein / Q000737:chemistry* / Q000378:metabolism*; D009363:Neoplasm Proteins; D011487:Protein Conformation; D012984:Software; D013229:Stearic Acids / Q000737:chemistry / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
chemical_list: D002352:Carrier Proteins; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D013229:Stearic Acids; D025521:Tumor Suppressor Proteins; C031183:stearic acid