64
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).
