Acetylcholinesterase: electrostatic steering increases the rate of ligand binding
| Autor: | James Andrew McCammon, Tan Rc, Joel L. Sussman, Thanh N. Truong |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Quantitative Biology::Biomolecules
Chemistry Charge (physics) Ligands Torpedo Ligand (biochemistry) Biochemistry Acetylcholine Diffusion Quantitative Biology::Subcellular Processes Reaction rate constant Ionic strength Computational chemistry Chemical physics Electric field Acetylcholinesterase Electrochemistry Brownian dynamics Acridines Animals Poisson's equation Brownian motion |
| Zdroj: | Biochemistry. 32:401-403 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi00053a003 |
| Popis: | Brownian dynamics simulations have been used to calculate the diffusion-controlled rate constants for the binding of a positively charged ligand to several models of acetylcholinesterase (AChE). The crystal structure was used to define the detailed topography and the active sites of the dimeric enzyme. The electric field around AChE was then computed by solving the Poisson equation for different charge distributions in the enzyme at zero ionic strength. These fields were used in turn to calculate the forces on the diffusing ligand. Significant increases in the rate constant resulted in going from a model with no charges to one with the net charges concentrated at the centers of the monomers and then to a model with a realistic distribution of charges throughout the enzyme. The results show that electrostatic steering of ligands contributes to the high rate constants that are observed experimentally for AChE. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|