CONFORMATIONAL TRANSITION PATHWAYS EXPLORED BY MONTE CARLO SIMULATION INTEGRATED WITH COLLECTIVE MODES Export

@article{citeulike:3365883, abstract = {Conformational transitions between open/closed or free/bound states in proteins bear functional importance. We propose a new technique (ANM-MC), in which the collective modes obtained from anisotropic network model (ANM) are used in conjunction with a Monte Carlo (MC) simulation approach to investigate conformational transition pathways and pathway intermediates. ANM-MC 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 (T)-relaxed (R2) forms of hemoglobin (C{alpha}-root mean square deviation (RMSD) between two end structures being 7.13 A and 3.55 A, respectively). Target conformations are reached by RMSD of 2.27 A and 1.90 A for AK and hemoglobin, respectively. The intermediate conformations overlap with crystal structures from AK family within 3.0 A RMSD. In the case of hemoglobin, the transition of T-to-R2 is shown to pass through the R state. In both cases, lowest frequency modes are effective during transitions. Targeted Monte Carlo (TMC) approach is also utilized without application of collective modes. Both ANM-MC and TMC can explore the sequence of events in the transition pathways with an efficient yet realistic conformational search. 10.1529/biophysj.107.128447}, author = {Kantarci-Carsibasi, Nigar and Haliloglu, Turkan and Doruker, Pemra}, citeulike-article-id = {3365883}, citeulike-linkout-0 = {http://dx.doi.org/10.1529/biophysj.107.128447}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0006349508820024}, citeulike-linkout-2 = {http://www.biophysj.org/cgi/content/abstract/95/12/5862?etoc}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/18676657}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=18676657}, day = {1}, doi = {10.1529/biophysj.107.128447}, journal = {Biophys. J.}, keywords = {conformation, monte\_carlo}, month = {August}, pages = {biophysj.107.128447+}, posted-at = {2008-10-14 21:15:50}, priority = {2}, title = {CONFORMATIONAL TRANSITION PATHWAYS EXPLORED BY MONTE CARLO SIMULATION INTEGRATED WITH COLLECTIVE MODES}, url = {http://dx.doi.org/10.1529/biophysj.107.128447}, year = {2008} }

TY - JOUR ID - citeulike:3365883 L3 - citeulike-article-id:3365883 N2 - Conformational transitions between open/closed or free/bound states in proteins bear functional importance. We propose a new technique (ANM-MC), in which the collective modes obtained from anisotropic network model (ANM) are used in conjunction with a Monte Carlo (MC) simulation approach to investigate conformational transition pathways and pathway intermediates. ANM-MC 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 (T)-relaxed (R2) forms of hemoglobin (C{alpha}-root mean square deviation (RMSD) between two end structures being 7.13 A and 3.55 A, respectively). Target conformations are reached by RMSD of 2.27 A and 1.90 A for AK and hemoglobin, respectively. The intermediate conformations overlap with crystal structures from AK family within 3.0 A RMSD. In the case of hemoglobin, the transition of T-to-R2 is shown to pass through the R state. In both cases, lowest frequency modes are effective during transitions. Targeted Monte Carlo (TMC) approach is also utilized without application of collective modes. Both ANM-MC and TMC can explore the sequence of events in the transition pathways with an efficient yet realistic conformational search. 10.1529/biophysj.107.128447 JF - Biophys. J. TI - CONFORMATIONAL TRANSITION PATHWAYS EXPLORED BY MONTE CARLO SIMULATION INTEGRATED WITH COLLECTIVE MODES SP - biophysj.107.128447 KW - conformation KW - monte_carlo AU - Kantarci-Carsibasi, Nigar AU - Haliloglu, Turkan AU - Doruker, Pemra PY - 2008/08/01/ UR - http://dx.doi.org/10.1529/biophysj.107.128447 ER -