title: New force field for calcium binding sites in annexin-membrane complexes.
abstract: For accurate classical molecular dynamics (MD) simulations of the calcium mediated bound complexes of annexin and membrane we have developed new force-field parameters correctly describing the interaction of the Ca ion with its environment. We have used quantum chemical calculations to investigate the potential energy surface experienced by the Ca ion within the three different binding sites found in domain 1 of annexin V (ANX V/1). Based on these calculations we were able to quantify the charge polarization of atoms within the binding sites, and to determine the geometry and force constants of harmonic restraints between the Ca ion and its coordinating oxygen atoms. Harmonic restraints were introduced to compensate for the deviations between the quantum mechanical potential energy surface and that of the classical force field. Our analysis has shown that using the refined force field for the Ca binding sites enables long-time MD simulations that conserve the initial structure of ANX V/1 significantly better than MD simulations using the standard force field.
authors.affiliation: National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia. franc@cmm.ki.si
authors.forename: Franci
authors.initials: F
authors.lastname: Merzel
authors.forename: Milan
authors.initials: M
authors.lastname: Hodoscek
authors.forename: Dusanka
authors.initials: D
authors.lastname: Janezic
authors.forename: Alain
authors.initials: A
authors.lastname: Sanson
mesh_terms: D017304:Annexin A5 / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D008958:Models, Molecular; D010718:Phosphatidylserines / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011789:Quantum Theory; D013499:Surface Properties; D014867:Water / Q000737:chemistry
chemical_list: D017304:Annexin A5; D010718:Phosphatidylserines; D014867:Water; D002118:Calcium