title: Conformational transition pathways explored by Monte Carlo simulation integrated with collective modes.
abstract: Conformational transitions between open/closed or free/bound states in proteins possess functional importance. We propose a technique in which the collective modes obtained from an anisotropic network model (ANM) are used in conjunction with a Monte Carlo (MC) simulation approach, to investigate conformational transition pathways and pathway intermediates. The ANM-MC technique is applied to adenylate kinase (AK) and hemoglobin. The iterative method, in which normal modes are continuously updated during the simulation, proves successful in accomplishing the transition between open-closed conformations of AK and tense-relaxed forms of hemoglobin (C(alpha)-root mean square deviations between two end structures of 7.13 A and 3.55 A, respectively). Target conformations are reached by root mean-square deviations of 2.27 A and 1.90 A for AK and hemoglobin, respectively. The intermediate conformations overlap with crystal structures from the AK family within a 3.0-A root mean-square deviation. In the case of hemoglobin, the transition of tense-to-relaxed passes through the relaxed state. In both cases, the lowest-frequency modes are effective during transitions. The targeted Monte Carlo approach is used without the application of collective modes. Both the ANM-MC and targeted Monte Carlo techniques can explore sequences of events in transition pathways with an efficient yet realistic conformational search.
authors.affiliation: Department of Chemical Engineering and Polymer Research Center, Bogazici University, Bebek 34342, Istanbul, Turkey.
authors.forename: Nigar
authors.initials: N
authors.lastname: Kantarci-Carsibasi
authors.forename: Turkan
authors.initials: T
authors.lastname: Haliloglu
authors.forename: Pemra
authors.initials: P
authors.lastname: Doruker
mesh_terms: D000263:Adenylate Kinase / Q000737:chemistry; D004926:Escherichia coli / Q000201:enzymology; D006454:Hemoglobins / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D009010:Monte Carlo Method; D016571:Neural Networks, Computer; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D006454:Hemoglobins; D011506:Proteins; D000263:Adenylate Kinase