title: Diffusion-influenced ligand binding to buried sites in macromolecules and transmembrane channels.
abstract: We consider diffusion-influenced binding to a buried binding site that is connected to the surface by a narrow tunnel. Under the single assumption of an equilibrium distribution of ligands over the tunnel cross section, we reduce the calculation of the time-dependent rate coefficient to the solution of a one-dimensional diffusion equation with appropriate boundary conditions. We obtain a simple analytical expression for the steady-state rate that depends on the potential of mean force in the tunnel and the diffusion-controlled rate of binding to the tunnel entrance. Potential applications of our theory include substrate binding to a buried active site of an enzyme and permeant ion binding to an internal site in a transmembrane channel.
authors.affiliation: Mathematical and Statistical Computing Laboratory, Division of Computational Bioscience, Center for Information Technology, National Institutes of Health, Bethesda, Maryland 20892, USA. berezh@mail.nih.gov
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Berezhkovskii
authors.forename: Attila
authors.initials: A
authors.lastname: Szabo
authors.forename: Huan-Xiang
authors.initials: HX
authors.lastname: Zhou
mesh_terms: D001665:Binding Sites; D004058:Diffusion; D008024:Ligands; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D011485:Protein Binding
chemical_list: D008024:Ligands; D046911:Macromolecular Substances; D026901:Membrane Transport Proteins