title: Effects of counter-ions and volume on the simulated dynamics of solvated proteins. Application to the activation domain of procarboxypeptidase B.
abstract: Molecular dynamics (MD) simulations of the globular activation domain of porcine procarboxypeptidase B (ADBp) and its isolated alpha-helix 1 were performed in order to understand the effects of adding salts and using periodic boundary conditions (this being reflected in the box size) along the simulations. alpha-Helix 1 was chosen because it is the most charged element of the secondary structure within ADBp. Different types of MD simulations with the GROMOS package were performed, studying either the whole activation domain or the isolated alpha-helix 1 with different water box sizes and counter-ionic shells. The analyses of the trajectories show that simulations of solvated proteins are highly sensitive to the presence of counter-ions and less sensitive to the volume of the water box. The differences in protein potential energies, r.m.s. deviations and radius of gyration between the simulations with and without counter-ions demonstrate that during such studies secondary structures of proteins are more stable when their charges are carefully neutralized. This stresses the need for such a procedure when analysing significantly charged proteins. The results also showed that the enlargement of the water box helps in the stabilization of the system.
authors.affiliation: Institut de Biologia Fonamental and Departament de Bioquímica, Universitat Autònoma de Barcelona, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Martí-Renom
authors.forename: J M
authors.initials: JM
authors.lastname: Mas
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
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D043424:Carboxypeptidase B; D002268:Carboxypeptidases / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D004792:Enzyme Precursors / Q000737:chemistry* / Q000378:metabolism; D004795:Enzyme Stability; D006860:Hydrogen Bonding; D007477:Ions; D008958:Models, Molecular; D009994:Osmolar Concentration; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012995:Solubility; D012997:Solvents; D013552:Swine; D013696:Temperature; D013816:Thermodynamics; D013997:Time Factors; D017186:Titrimetry; D014867:Water / Q000378:metabolism
chemical_list: D000596:Amino Acids; D004792:Enzyme Precursors; D007477:Ions; D012997:Solvents; D014867:Water; D002268:Carboxypeptidases; D043424:Carboxypeptidase B