Speaker:Amarda Shehu, Department of Computer Science, George Mason University
Title: Of Protein Structures and Motions: Probabilistic Search and Optimization

Abstract: Many computational issues related to modeling of physical systems benefit from search and optimization techniques. Our work shows how such techniques, shown useful in other domains, such as robotics motion planning and evolutionary computing, can be adapted to advance the state of modeling and simulation in computational structural biology. Our application focus is on elucidating structures and motions employed by protein systems for biological activity, as this is central to understanding biology and disease. Our work shows how ideas from evolutionary computation allow modeling the biologically-active structure of a protein from its amino acid sequence or the bound structure of a protein dimer from the unbound rigid monomeric structures. A novel robotics-inspired probabilistic search framework is shown versatile and effective both in modeling structures and transitions between them. The framework employs projections of the search space in order to adaptively guide its exploration and further computational resources to relevant regions of the search space. Applications and analyses on diverse small-to-medium size proteins show enhanced sampling of the conformational space and effective modeling of biologically-active structures. In addition, conformational transitions are obtained that connect functional states of significant structural dissimilarity in moonlighting protein systems.

Time: Friday, November 2, 2012, 1:30-2:30 p.m.

Place: Planetary Hall (formerly S & T I), Room 242

Department of Mathematical Sciences
George Mason University
4400 University Drive, MS 3F2
Fairfax, VA 22030-4444
Tel. 703-993-1460, Fax. 703-993-1491