title: Extension of a protein docking algorithm to membranes and applications to amyloid precursor protein dimerization.
abstract: Novel adjustments are introduced to the docking algorithm, DOCK/PIERR, for the purpose of predicting structures of transmembrane protein complexes. Incorporating knowledge about the membrane environment is shown to significantly improve docking accuracy. The extended version of DOCK/PIERR is shown to perform comparably to other leading docking packages. This membrane version of DOCK/PIERR is applied to the prediction of coiled-coil homodimer structures of the transmembrane region of the C-terminal peptide of amyloid precursor protein (C99). Results from MD simulation of the C99 homodimer in POPC bilayer and docking are compared. Docking results are found to capture key aspects of the homodimer ensemble, including the existence of three topologically distinct conformers. Furthermore, the extended version of DOCK/PIERR is successful in capturing the effects of solvation in membrane and micelle. Specifically, DOCK/PIERR reproduces essential differences in the homodimer ensembles simulated in POPC bilayer and DPC micelle, where configurational entropy and surface curvature effects bias the handedness and topology of the homodimer ensemble.
authors.affiliation: Department of Computer Science, University of Texas at Austin, Austin, Texas, 78712.|Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, Texas, 78712.
authors.forename: Shruthi
authors.initials: S
authors.lastname: Viswanath
authors.affiliation: Department of Chemistry, Boston University, Boston, Massachusetts, 02215.
authors.forename: Laura
authors.initials: L
authors.lastname: Dominguez
authors.affiliation: Department of Chemistry, Boston University, Boston, Massachusetts, 02215.
authors.forename: Leigh S
authors.initials: LS
authors.lastname: Foster
authors.affiliation: Department of Chemistry, Boston University, Boston, Massachusetts, 02215.
authors.forename: John E
authors.initials: JE
authors.lastname: Straub
authors.affiliation: Institute for Computational Engineering and Sciences, University of Texas at Austin, Austin, Texas, 78712.|Department of Chemistry, University of Texas at Austin, Austin, Texas, 78712.
authors.forename: Ron
authors.initials: R
authors.lastname: Elber
mesh_terms: D000465:Algorithms; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D019277:Entropy; D008051:Lipid Bilayers; D008823:Micelles; D062105:Molecular Docking Simulation / Q000379:methods*; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry; D055503:Protein Multimerization
chemical_list: D016564:Amyloid beta-Protein Precursor; D008051:Lipid Bilayers; D008823:Micelles; D010713:Phosphatidylcholines; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
keywords: all-atom MD simulation; amyloid precursor protein; explicit and implicit solvent; membrane potential; micelle and bilayer environments; protein-protein docking; transmembrane complexes