title: Novel scoring function for modeling structures of oligomers of transmembrane alpha-helices.
abstract: Specific non-covalent interactions between transmembrane (TM) alpha-helices are important in a variety of biological processes. Experimental and computational studies have shown that van der Waals interactions play an important role in the tight packing between TM alpha-helices, although polar interactions can also be important in some instances. Based on the assumption that van der Waals interaction alone is sufficient for a meso-scale (residue-scale) description of the interaction between TM alpha-helices, we have designed a novel residue-scale scoring function for modeling structures of oligomers of TM alpha-helices. We first calculated atomistic van der Waals interaction energies between two amino acids, X and Y, of a pair of parallel alpha-helices, glycine-X-glycine and glycine-Y-glycine and compiled them according to three variables, the distance between the two C(alpha) atoms and the rotational angles of X and Y about their helical axes. Upon averaging over the rotational angles, we obtained one-dimensional interaction energy profiles that are functions of the distance between C(alpha) atoms only. Each of the interaction energy profiles was fitted with a generic fitting function of the distance between C(alpha) atoms, yielding analytical scoring functions for all possible amino acid pairs. For glycophorin A, neu/erbB-2, and phospholamban, lowest-energy conformations obtained through exhaustive scanning of the entire conformational space using the scoring functions were compatible with available experimental data.
authors.affiliation: Center for Bioinformatics, Unversity of Saarland, 66041 Saarbruecken, Germany.
authors.forename: Yungki
authors.initials: Y
authors.lastname: Park
authors.forename: Markus
authors.initials: M
authors.lastname: Elsner
authors.forename: Rene
authors.initials: R
authors.lastname: Staritzbichler
authors.forename: Volkhard
authors.initials: V
authors.lastname: Helms
mesh_terms: D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D006021:Glycophorins / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D006021:Glycophorins; D008565:Membrane Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000099211:Phospholamban