Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery: Bridging Experiments and Computations - September 10-14, 2014, Istanbul, Turkey

Modeling of Biomolecular Systems Interactions, Dynamics, and Allostery Poster Session II

88-POS Board 41 Generation of Conformational Transition Pathways and the Prediction of Closed Structure for Proteins Arzu Uyar , Nigar Kantarci-Carsibasi, Turkan Haliloglu, Pemra Doruker. Bogazici University, Istanbul, Bebek, Turkey. Conformational transition pathways between open and closed crystal structures were produced for a set of 20 proteins using a hybrid simulation technique, named as ANM-MC. This iterative technique generates a targeted pathway between two conformations, where the collective modes from the anisotropic network model (ANM) are used for deformation at each iteration and the energy of the deformed structure is minimized via local moves using a knowledge-based Monte Carlo (MC) algorithm. Our data set consists of 9 hinge-bending-type proteins (initial RMSDs = 4-12 Å), 6 DNA-binding proteins (RMSD = 3-9 Å), and 5 enzymes with functional loop closure (loop RMSD = 3-14.5 Å). We observe successful approaches to target, with at least 50% decrease in RMSDs, for 17 of proteins studied. For proteins showing a significant change in radius of gyration (Rg) during the conformational transition, deforming along a single predominant mode (first or second) in the decreasing Rg direction leads to successful predictions of target structure for 7 out of 9 hinge-bending-type proteins (2.0-2.9 Å final RMSDs to target) and for two DNA-binding proteins (1.5 and 1.7 Å). Based on previously reported free energy surface of adenylate kinase, deformations along the first mode produced an energetically favorable path, which is interestingly facilitated by mode swapping at key points. Similar changes in slow mode shapes were also observed in other proteins during the transitions.

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