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 IX Abstracts

Effect of Ligand Binding on Enzyme Global Dynamics and Function Pemra Doruker . Bogazici University, Istanbul, Turkey.

The link between enzyme dynamics and catalytic activity can be facilitated through computational means. Such studies based on elastic network models (ENM) and molecular dynamics (MD) simulations will be presented in this talk. In the case of enzymes with functional loops that close over the active site during catalysis, the seemingly localized conformational changes of these loops are in fact coupled to the global ENM or essential MD modes of motion. For the specific case of triosephosphate isomerase (TIM), the functional, dimeric topology drives loop opening/closure as opposed to the monomeric TIM with reduced catalytic activity. Thus, collective modes dictated by the enzyme topology seem to guide its functional loop dynamics, which is critical for substrate entrance, product release and catalysis. Binding of ligands to specific sites on an enzyme act as constraints on its network of interactions, thereby affecting its vibrational dynamics to various extents. For example, binding of certain allosteric inhibitors at TIM’s subunit interface alters global modes and enzyme activity significantly. In this respect, the extent to which different type of ligands, including allosteric and orthosteric ones, modify the low-frequency vibrational modes of enzymes can be determined by mixed resolution ENM. Such an approach can be further utilized for isolating among alternative ligand binding positions/poses those that have an effect on enzyme global dynamics.

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