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 I

10-POS Board 10 Local and Allosteric Effects Due to Displacement, Force and Mutation Induced Perturbations on Calmodulin and Hsp70 Ayse O. Aykut 1,2 , Gizem Ozbaykal 2 , Canan Atilgan 2 , Ali R. Atilgan 2 . 1 University of Basel, Basel, Switzerland, 2 Sabanci University, Istanbul, Turkey. We investigate how perturbations that may be experienced by proteins in their fluctuating environments may be invoked to facilitate their access to different microstates, using the example of calmodulin[1] and Hsp70[2]. We introduce perturbations that are explored within the neighborhood of the local minima of the protein by (i) exerting external forces applied (PRS)[3], (ii) selected displacements[4], (iii) mutating each residue to alanine[2]. In (i), we operate under the linear response assumption and the kernel of this approach is the variance-covariance matrix obtained from all-atom molecular dynamics simulations. In (ii), external displacements are introduced such that the observed changes remain in the linear response regime. By minimizing the protein-water system under this constraint, all other atoms are allowed to re-arrange around the perturbed geometry. In (iii), selected residues are mutated to alanine, followed by energy minimization. This procedure also allows the protein-water system to respond around the perturbed geometry, revising the local interactions occurring due to the mutated residue. In all approaches, residues that led to the best overlaps with the experimentally determined conformational change are further analyzed to explore their relation to protein structure and function. Each method has a different perspective of inherent assumptions and the interactions accentuated by each vary. The differences between these methods are compared in terms of interactions, dominating forces in the response of the system, and key residues on the protein structure that are implicated by each approach. [1] A.O. Aykut, A.R. Atilgan, and C. Atilgan, PLoS Comput. Biol., 9, 12, (2013). [2] G. Ozbaykal, C. Atilgan, and A. R. Atilgan, to appear.(2014). [3] C. Baysal and A. R. Atilgan, Proteins, 45, 62 (2001). [4] C. Atilgan and A. R. Atilgan, PLoS Comput. Biol., 5, e1000544 (2009).

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