title: Prediction of solution structures of the Ca2+-bound gamma-carboxyglutamic acid domains of protein S and homolog growth arrest specific protein 6: use of the particle mesh Ewald method.
abstract: The solution structures of the N-terminal domains of protein S, a plasma vitamin K-dependent glycoprotein, and its homolog growth arrest specific protein 6 (Gas6) were predicted by molecular dynamics computer simulations. The initial structures were based on the x-ray crystallographic structure of the corresponding region of bovine prothrombin fragment 1. The subsequent molecular dynamics trajectories were calculated using the second-generation AMBER force field. The long-range electrostatic forces were evaluated by the particle mesh Ewald method. The structures that stabilized over a 400-ps time interval were compared with the corresponding region of the simulated solution structure of bovine prothrombin fragment 1. Structural properties of the gamma-carboxyglutamic acid (Gla) domains obtained from simulations and calcium binding were found to be conserved for all three proteins. Analysis of the predicted solution structure of the Gla domain of Gas6 suggests that this domain should bind with negatively charged phospholipid surfaces analogous to bovine prothrombin fragment 1 and protein S.
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill 27599-3290, USA.
authors.forename: L
authors.initials: L
authors.lastname: Perera
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Darden
authors.forename: D M
authors.initials: DM
authors.lastname: Monroe
authors.forename: L G
authors.initials: LG
authors.lastname: Pedersen
mesh_terms: D015055:1-Carboxyglutamic Acid / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D002118:Calcium / Q000737:chemistry; D002417:Cattle; D003198:Computer Simulation; D006801:Humans; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D010743:Phospholipids / Q000737:chemistry; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics; D017293:Protein S / Q000737:chemistry* / Q000235:genetics; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D011516:Prothrombin / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D055672:Static Electricity; D013816:Thermodynamics; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D015055:1-Carboxyglutamic Acid; D002118:Calcium; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010743:Phospholipids; D011498:Protein Precursors; D017293:Protein S; D011506:Proteins; D011516:Prothrombin; D012996:Solutions; D000099255:Growth Arrest-Specific Protein 6; C029733:prothrombin fragment 1