The rate of protein-protein association limits the response time due
to protein-protein interactions. The bimolecular association rate
may be diffusion-controlled or influenced, and in such cases, Brownian
dynamics simulations of protein-protein diffusional association may
be used to compute association rates. Here, we report Brownian dynamics
simulations of the diffusional association of five different protein-protein
pairs: barnase and barstar, acetylcholinesterase and fasciculin-2,
cytochrome c peroxidase and cytochrome c, the HyHEL-5 antibody and
hen egg lysozyme (HEL), and the HyHEL-10 antibody and HEL. The same
protocol was used to compute the diffusional association rates for
all the protein pairs in order to assess, by comparison to experimentally
measured rates, whether the association of these proteins can be
explained solely on the basis of diffusional encounter. The simulation
protocol is similar to those previously derived for simulation of
the association of barnase and barstar, and of acetylcholinesterase
and fasciculin-2; these produced results in excellent agreement with
experimental data for these protein pairs, with changes in association
rate due to mutations reproduced within the limits of expected computational
and modeling errors. Here, we find that for all protein pairs, the
effects of mutations can be well reproduced by the simulations, even
though the degree of the electrostatic translational and orientational
steering varies widely between the cases. However, the absolute values
of association rates for the acetylcholinesterase: fasciculin-2 and
HyHEL-10 antibody: HEL pairs are overestimated. Comparison of bound
and unbound protein structures shows that this may be due to gating
resulting from protein flexibility in some of the proteins. This
may lower the association rates compared to their bimolecular diffusional
encounter rates.
%0 Journal Article
%1 Gabd_2001_1139
%A Gabdoulline, R. R.
%A Wade, R. C.
%D 2001
%J J. Mol. Biol.
%K 11237623 Acetylcholinesterase, Bacterial Binding, Chemical, Comparative Computer Concentration, Conformation, Cy, Cytochrome Cytochromes Cytochromes, Egg Elapid Electron Electrostatics, Gov't, Group, Hydrogen-Ion Ligands, Models, Molecular, Mutation, Non-U.S. Oxidation-Reduction, Oxygen, Peroxidase, Plastocyanin, Point Protein Proteins, Research Ribonucleases, Secondary, Simulation, Spinacia Statistical, Structure, Study, Support, Tertiary, Transport, Venoms, c f, oleracea, tochrome-c
%N 5
%P 1139--1155
%R 10.1006/jmbi.2000.4404
%T Protein-protein association: investigation of factors influencing
association rates by brownian dynamics simulations.
%U http://dx.doi.org/10.1006/jmbi.2000.4404
%V 306
%X The rate of protein-protein association limits the response time due
to protein-protein interactions. The bimolecular association rate
may be diffusion-controlled or influenced, and in such cases, Brownian
dynamics simulations of protein-protein diffusional association may
be used to compute association rates. Here, we report Brownian dynamics
simulations of the diffusional association of five different protein-protein
pairs: barnase and barstar, acetylcholinesterase and fasciculin-2,
cytochrome c peroxidase and cytochrome c, the HyHEL-5 antibody and
hen egg lysozyme (HEL), and the HyHEL-10 antibody and HEL. The same
protocol was used to compute the diffusional association rates for
all the protein pairs in order to assess, by comparison to experimentally
measured rates, whether the association of these proteins can be
explained solely on the basis of diffusional encounter. The simulation
protocol is similar to those previously derived for simulation of
the association of barnase and barstar, and of acetylcholinesterase
and fasciculin-2; these produced results in excellent agreement with
experimental data for these protein pairs, with changes in association
rate due to mutations reproduced within the limits of expected computational
and modeling errors. Here, we find that for all protein pairs, the
effects of mutations can be well reproduced by the simulations, even
though the degree of the electrostatic translational and orientational
steering varies widely between the cases. However, the absolute values
of association rates for the acetylcholinesterase: fasciculin-2 and
HyHEL-10 antibody: HEL pairs are overestimated. Comparison of bound
and unbound protein structures shows that this may be due to gating
resulting from protein flexibility in some of the proteins. This
may lower the association rates compared to their bimolecular diffusional
encounter rates.
@article{Gabd_2001_1139,
abstract = {The rate of protein-protein association limits the response time due
to protein-protein interactions. The bimolecular association rate
may be diffusion-controlled or influenced, and in such cases, Brownian
dynamics simulations of protein-protein diffusional association may
be used to compute association rates. Here, we report Brownian dynamics
simulations of the diffusional association of five different protein-protein
pairs: barnase and barstar, acetylcholinesterase and fasciculin-2,
cytochrome c peroxidase and cytochrome c, the HyHEL-5 antibody and
hen egg lysozyme (HEL), and the HyHEL-10 antibody and HEL. The same
protocol was used to compute the diffusional association rates for
all the protein pairs in order to assess, by comparison to experimentally
measured rates, whether the association of these proteins can be
explained solely on the basis of diffusional encounter. The simulation
protocol is similar to those previously derived for simulation of
the association of barnase and barstar, and of acetylcholinesterase
and fasciculin-2; these produced results in excellent agreement with
experimental data for these protein pairs, with changes in association
rate due to mutations reproduced within the limits of expected computational
and modeling errors. Here, we find that for all protein pairs, the
effects of mutations can be well reproduced by the simulations, even
though the degree of the electrostatic translational and orientational
steering varies widely between the cases. However, the absolute values
of association rates for the acetylcholinesterase: fasciculin-2 and
HyHEL-10 antibody: HEL pairs are overestimated. Comparison of bound
and unbound protein structures shows that this may be due to gating
resulting from protein flexibility in some of the proteins. This
may lower the association rates compared to their bimolecular diffusional
encounter rates.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Gabdoulline, R. R. and Wade, R. C.},
biburl = {https://www.bibsonomy.org/bibtex/2c545e67d59c22dfc393025870e84e5e5/hake},
description = {The whole bibliography file I use.},
doi = {10.1006/jmbi.2000.4404},
file = {Gabd_2001_1139.pdf:Gabd_2001_1139.pdf:PDF},
interhash = {ab31e760eb273857a0cdc8df8477835b},
intrahash = {c545e67d59c22dfc393025870e84e5e5},
journal = {J. Mol. Biol.},
keywords = {11237623 Acetylcholinesterase, Bacterial Binding, Chemical, Comparative Computer Concentration, Conformation, Cy, Cytochrome Cytochromes Cytochromes, Egg Elapid Electron Electrostatics, Gov't, Group, Hydrogen-Ion Ligands, Models, Molecular, Mutation, Non-U.S. Oxidation-Reduction, Oxygen, Peroxidase, Plastocyanin, Point Protein Proteins, Research Ribonucleases, Secondary, Simulation, Spinacia Statistical, Structure, Study, Support, Tertiary, Transport, Venoms, c f, oleracea, tochrome-c},
month = Mar,
number = 5,
pages = {1139--1155},
pii = {S0022-2836(00)94404-8},
pmid = {11237623},
timestamp = {2009-06-03T11:21:12.000+0200},
title = {Protein-protein association: investigation of factors influencing
association rates by brownian dynamics simulations.},
url = {http://dx.doi.org/10.1006/jmbi.2000.4404},
volume = 306,
year = 2001
}