Abstract
Protein association events are ubiquitous in biological systems. Some
protein associations and subsequent responses are diffusion controlled
in vivo. Hence, it is important to be able to compute bimolecular
diffusional association rates for proteins. The Brownian dynamics
simulation methodology may be used to simulate protein-protein encounter,
compute association rates, and examine their dependence on protein
mutation and the nature of the physical environment (e.g., as a function
of ionic strength or viscosity). Here, the theory for Brownian dynamics
simulations is described, and important methodological aspects, particularly
pertaining to the correct modeling of electrostatic forces and definition
of encounter complex formation, are highlighted. To illustrate application
of the method, simulations of the diffusional encounter of the extracellular
ribonuclease, barnase, and its intracellular inhibitor, barstar,
are described. This shows how experimental rates for a series of
mutants and the dependence of rates on ionic strength can be reproduced
well by Brownian dynamics simulations. Potential future uses of the
Brownian dynamics method for investigating protein-protein association
are discussed.
- 3-phosphate,
- 9571088
- animals,
- bacterial
- binding
- binding,
- brucei
- brucei,
- cerevisiae,
- chemical,
- chickens,
- coli,
- comparative
- computer
- diffusion,
- dismutase,
- electrostatics,
- escherichia
- fungal
- glyceraldehyde
- gov't,
- humans,
- ions,
- isomerase,
- ligands,
- models,
- molecular,
- non-u.s.
- protein
- proteins,
- protozoan
- research
- ribonucleases,
- saccharomyces
- simulation,
- sites,
- software,
- species
- specificity,
- study,
- substrate
- superoxide
- support,
- thermodynamics,
- triose-phosphate
- trypanosoma
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