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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.
