ISSN:
0020-7608
Keywords:
Computational Chemistry and Molecular Modeling
;
Atomic, Molecular and Optical Physics
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The Brownian dynamics simulation method has been developed as an alternative to conventional molecular dynamics or simple analytical diffusion theories in order to study the diffusive dynamics and interaction between two whole proteins. Highly detailed and realistic models of protein structures and their electrostatic interactions were used based on an atomic-level spatial description. The Coulombic and excluded volume torques and forces between the molecules are computed at each Brownian time step and rotational and translational diffusional trajectories are generated between interacting proteins. For the first time the rotation of both proteins is included. This method has been applied to study the association and electron transfer between horse heart ferrocytochrome c and yeast cytochrome c peroxidase, horse heart ferricytochrome c and bovine ferrocytochrome b5 and the electron self-exchange of P. aeruginosa cytochrome c551. Accurate residue charge assignments at the appropriate pH and ionic strength are computed by the Tanford-Kirkwood theory with surface accessibility modification. Accurate interaction potentials are computed by iterating solutions of the Poisson-Boltzmann equation on a grid. The low dielectric constant inside proteins, electrolyte screening effects, and irregular protein surface topography are taken into account. Realistic criteria for determining the successful docking of the cytochromes are based on a combination of mutual orientation of heme planes and heme edge-to-edge distance. We examine the role of electrostatic charge distribution and solvent mediation in the facilitation of protein-protein docking prior to the electron transfer step. We expect that, with improvements, the Brownian dynamics method will be capable of predicting the effects of site-directed mutagenesis on protein-protein and protein-ligand interactions.
Additional Material:
5 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/qua.560381709
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