title: Mechanisms of selectivity in channels and enzymes studied with interactive molecular dynamics.
abstract: Interactive molecular dynamics, a new modeling tool for rapid investigation of the physical mechanisms of biological processes at the atomic level, is applied to study selectivity and regulation of the membrane channel protein GlpF and the enzyme glycerol kinase. These proteins facilitate the first two steps of Escherichia coli glycerol metabolism. Despite their different function and architecture the proteins are found to employ common mechanisms for substrate selectivity: an induced geometrical fit by structurally homologous binding sites and an induced rapid dipole moment reversal. Competition for hydrogen bonding sites with water in both proteins is critical for substrate motion. In glycerol kinase, it is shown that the proposed domain motion prevents competition with water, in turn regulating the binding of glycerol.
authors.affiliation: Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Grayson
authors.forename: Emad
authors.initials: E
authors.lastname: Tajkhorshid
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulten
mesh_terms: D020346:Aquaporins / Q000737:chemistry*; D001665:Binding Sites; D002241:Carbohydrates / Q000737:chemistry*; D003196:Computer Graphics; D003198:Computer Simulation; D004798:Enzymes / Q000737:chemistry; D004926:Escherichia coli / Q000737:chemistry* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry*; D005990:Glycerol / Q000737:chemistry / Q000378:metabolism; D005991:Glycerol Kinase / Q000737:chemistry*; D015640:Ion Channel Gating / Q000502:physiology; D007473:Ion Channels / Q000737:chemistry; D007700:Kinetics; D008954:Models, Biological; D008956:Models, Chemical; D009038:Motion; D009862:Online Systems; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012255:Ribitol / Q000737:chemistry; D012680:Sensitivity and Specificity; D012984:Software; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013402:Sugar Alcohols / Q000737:chemistry; D014584:User-Computer Interface
chemical_list: D020346:Aquaporins; D002241:Carbohydrates; D004798:Enzymes; D029968:Escherichia coli Proteins; D007473:Ion Channels; D013402:Sugar Alcohols; C078043:GlpF protein, E coli; D012255:Ribitol; D005991:Glycerol Kinase; D005990:Glycerol; C014999:arabitol