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 Session VIII Abstracts

Sequence Variations and Allosteric Dynamics in Binding Turkan Haliloglu . Bogazici University, Istanbul, Turkey.

Proteins are of highly dynamic nature with a complex interrelation between structural dynamics and their binding behavior. With the capacity of assuming an ensemble of conformations, they perform local to global fluctuations to interact with others in a dynamic infrastructure adopted to functional motion. On the exemplary case studies, it will be presented how the sequence variations at hinge regions of most cooperative movements could be instrumental to allosterically affect the binding site dynamics or dispose alternative binding modes with a change in functionality. The long-range dissemination of the perturbations in local chemistry or physical interactions through an impact on global dynamics can reform the allosteric dynamics. The findings posits an aspect for the coupling of structural dynamics and evolvability in the modulation of protein interactions. Extracting Dynamics Information from Multiple Molecular Structures and Computationally Generating Their Transition Pathways Robert Jernigan 1 , Kannan Sankar 1 , Kejue Jia 1 , Jie Liu 1 , Yuan Wang 1 , Ataur Katebi 1 , Michael Zimmermann 2,1 . 1 Iowa State University, Ames, IA, USA, 2 Mayo Clinic College of Medicine, Rochester, MN, USA. Meaningful dynamics information can be extracted from multiple experimental structures of the same, or closely related, proteins or RNAs. The covariance matrix of atom positions is decomposable into principal components. Usually only a few principal components describe the motions of the structures, and these usually relate to the functional dynamics. This dynamics information provides strong evidence for the plasticity of protein and RNA structures, and also suggests that these structures almost always have a highly limited repertoire of motions. In some cases, such as many enzymes the dominant motions are opening and closing over the active site. For myoglobin the changes are smalle, reflecting in part the small changes in sequence, but nonetheless they show characteristic details in their motions that are species dependent. We are computing pathways for transitions between different conformations, by generating structures with a Metropolis Monte Carlo method, using free energies for structural intermediates computed using our 4-body potentials and entropies from elastic network models. These provide effective pathways that traverse the space of the experimental structures. In some other cases transitions can be initiated by exothermic reactions, and these transitions can be effected by application of forces at or near the reaction center. This work provides new tools that can be used to understand the sets of available structures.

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