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

From Polymer Rubberlike Elasticity to Protein Dynamics – How Simple Physical Models of Rubber Influenced Modern Biophysics Andrzej Kloczkowski . Nationwide Children's Hospital / The Ohio State University, Columbus, OH, USA. Elastic Network Models of proteins have their origins in the theory of rubberlike elasticity of polymer networks. I will discuss the historical context of development of the theory of rubberlike materials and contributions of Professor Burak Erman to this field. I will show how simple models of Gaussian phantom polymer networks were applied to study protein dynamics, with the specific emphasis on significant involvement and major contributions of Burak Erman and his collaborators to this area of research. In the later part of my talk I’ll show how fluctuational dynamics of proteins described by the normal mode analysis and elastic network models controls protein dynamics and can explain variety of physical processes, such as the order of breaking contacts during the mechanical unfolding of proteins, and the process of structural refinement of protein models in protein structure prediction. Allosteric Regulation of the Glycolytic Pathway in Mammals and Trypanosomes Malcolm Walkinshaw . Edinburgh University, Edinburgh, United Kingdom. The two most highly regulated enzymes in the glycolytic pathway are phosphofructokinase (PFK) and pyruvate kinase (PYK). Both enzymes are allosterically activated by a range of metabolites as well as by a number of poorly characterised covalent modifications including acetylation, phosphorylation and nitrosylation. In a dividing cell, glucose metabolites are required for protein and DNA synthesis. A delicate balance must be reached between allowing the pathway to burn glucose to generate ATP and providing building blocks for the growing cell. Both cancer cells and unicellular parasite share a craving for glucose to allow unrestrained growth. The enzyme mechanisms of PFK and PYK are closely conserved between trypanosomes and mammals however the control mechanisms regulating their activities have diverged significantly and make use of different classes of molecules including hormones, amino acids and nucleotides to allosterically activate or inhibit their enzyme activities. We have been studying the structures and kinetics of human and parasite PYK and PFK in order to understand the regulatory mechanisms at a molecular level and use this insight to design potential new therapeutic approaches to tackle proliferative and infective diseases.

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