title: On the induced-fit mechanism of substrate-enzyme binding structures of nylon-oligomer hydrolase.
abstract: We present a detailed computational investigation of the induced-fit motion in a nylon-oligomer hydrolase (NylB) upon substrate binding. To this aim, we resort on the recently introduced parallel cascade selection molecular dynamics approach, allowing for an accelerated access to the set of conformational changes from an open- to a closed-state structure to form the enzyme-substrate complex in a specific induce-fit mechanism. The structural investigation is quantitatively complemented by free energy analyses within the umbrella sampling algorithm accompanied by weighted histogram analysis. We find that the stabilization free energy is about 1.4 kcal/mol, whereas the highest free energy barrier to be overcome is about 2.3 kcal/mol. Conversely, the energetic contribution for the substrate binding is about 20 kcal/mol, as estimated from Generalized Born/Surface Area. This means that the open-close induced-fit motion could occur frequently once the substrate binds to the open state of NylB.
authors.affiliation: Department of Materials Engineering Science, Graduate School of Engineering Science, Osaka University, Toyonaka, 560-8531, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Baba
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Harada
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Nakano
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Shigeta
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D004798:Enzymes / Q000378:metabolism*; D008956:Models, Chemical; D011485:Protein Binding; D011487:Protein Conformation; D013379:Substrate Specificity; D013816:Thermodynamics
chemical_list: D004798:Enzymes; D000581:Amidohydrolases; C026250:6-aminohexanoate-dimer hydrolase
keywords: enzyme-substrate binding; free energy landscape; induced-fit; nylon-oligomer hydrolase NylB; parallel cascade selection molecular dynamics