141
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.
