title: On the sensitivity of MD trajectories to changes in water-protein interaction parameters: the potato carboxypeptidase inhibitor in water as a test case for the GROMOS force field.
abstract: A critical evaluation is presented of the sensitivity of the results of molecular dynamics simulations of proteins to changes in the parameters describing water-protein and protein-protein van der Waals interactions in the GROMOS force field. The origin of the van der Waals and electrostatic parameters of the GROMOS standard force field is reviewed, and possible weaknesses are discussed. Four alternate sets of van der Waals parameters for the oxygen types of the GROMOS force field that have been suggested by different authors are then tested against the original force field. Six 500 ps molecular dynamics simulations of the potato carboxypeptidase inhibitor (PCI) in solution using the different parameter sets are analyzed and the results compared with the available X-ray and NMR data. It is shown that the behavior of the molecular system is very sensitive to changes in the van der Waals parameters of the oxygens, especially when affecting the interactions between water and aliphatic or aromatic groups. It is also shown that correction of just the repulsive van der Waals parameter of the water oxygen for its interactions with nonpolar groups is sufficient to correct the main deficiency of the original GROMOS parameter set. Nevertheless, the present study suggest that further refinement of the current parameters is still needed for a proper representation of nonbonded interactions.
authors.affiliation: Institut de Biologia Fonamental, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors.forename: X
authors.initials: X
authors.lastname: Daura
authors.forename: B
authors.initials: B
authors.lastname: Oliva
authors.forename: E
authors.initials: E
authors.lastname: Querol
authors.forename: F X
authors.initials: FX
authors.lastname: Avilés
authors.forename: O
authors.initials: O
authors.lastname: Tapia
mesh_terms: D000465:Algorithms; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D043422:Carboxypeptidases A; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010940:Plant Proteins / Q000737:chemistry*; D011480:Protease Inhibitors / Q000737:chemistry* / Q000378:metabolism; D011198:Solanum tuberosum; D014867:Water / Q000378:metabolism
chemical_list: D010940:Plant Proteins; D011480:Protease Inhibitors; D014867:Water; D002268:Carboxypeptidases; D043422:Carboxypeptidases A