Electrostatic steering of substrate to acetylcholinesterase: analysis of field fluctuations.

Based on previous molecular dynamics simulation results for acetylcholinesterase dimer, we calculate and analyse the electrostatic field fluctuations around the enzyme. The results show that dynamic features of the electrostatic field favor attraction of the positively-charged substrate. An Internet link to an animation of the results is also provided.

[1]  A. Goldman,et al.  Atomic structure of acetylcholinesterase from Torpedo californica: a prototypic acetylcholine-binding protein , 1991, Science.

[2]  J. Briggs,et al.  A 240-fold electrostatic rate-enhancement for acetylcholinesterase-substrate binding can be predicted by the potential within the active site , 1996 .

[3]  J. Mccammon,et al.  Electrostatic Influence on the Kinetics of Ligand Binding to Acetylcholinesterase , 1997, The Journal of Biological Chemistry.

[4]  J A McCammon,et al.  Correlation between rate of enzyme-substrate diffusional encounter and average Boltzmann factor around active site. , 1998, Biopolymers.

[5]  P Taylor,et al.  The cholinesterases: from genes to proteins. , 1994, Annual review of pharmacology and toxicology.

[6]  L. R. Scott,et al.  Computer Modeling of Acetylcholinesterase and Acetylcholinesterase-Ligand Complexes , 1995 .

[7]  J A McCammon,et al.  Acetylcholinesterase: role of the enzyme's charge distribution in steering charged ligands toward the active site. , 1998, Biopolymers.

[8]  P. Taylor,et al.  Acetylcholinesterase inhibition by fasciculin: Crystal structure of the complex , 1995, Cell.

[9]  J. Mccammon,et al.  Conformation gating as a mechanism for enzyme specificity. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[10]  M. Gilson,et al.  Acetylcholinesterase: Effects of Ionic Strength and Dimerization on the Rate Constants , 1994 .

[11]  M. Gilson,et al.  Simulation of charge-mutant acetylcholinesterases. , 1995, Biochemistry.

[12]  L. R. Scott,et al.  Electrostatics and diffusion of molecules in solution: simulations with the University of Houston Brownian dynamics program , 1995 .

[13]  J L Sussman,et al.  Open "back door" in a molecular dynamics simulation of acetylcholinesterase. , 1994, Science.

[14]  Electrostatic attraction by surface charge does not contribute to the catalytic efficiency of acetylcholinesterase. , 1994 .

[15]  D. Quinn,et al.  Acetylcholinesterase: enzyme structure, reaction dynamics, and virtual transition states , 1987 .

[16]  J A McCammon,et al.  Analysis of synaptic transmission in the neuromuscular junction using a continuum finite element model. , 1998, Biophysical journal.

[17]  P Taylor,et al.  Rapid binding of a cationic active site inhibitor to wild type and mutant mouse acetylcholinesterase: Brownian dynamics simulation including diffusion in the active site gorge. , 1998, Biopolymers.

[18]  J. Andrew McCammon,et al.  Molecular Dynamics of Acetylcholinesterase Dimer Complexed with Tacrine , 1997 .

[19]  J L Sussman,et al.  Acetylcholinesterase: electrostatic steering increases the rate of ligand binding. , 1993, Biochemistry.

[20]  J A McCammon,et al.  Mouse acetylcholinesterase unliganded and in complex with huperzine A: a comparison of molecular dynamics simulations. , 1999, Biopolymers.

[21]  Palmer Taylor,et al.  Enzymes of the Cholinesterase Family , 1995, Springer US.

[22]  F. Young.  Biochemistry , 1955, The Indian Medical Gazette.