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Atomistic and Coarse-Grained Simulations of Nucleosomes, Proteins and DNA

Monday, October 3, 2PM – 3PM
POB 6.304

Garegin A. Papoian

Structural physical modeling of biologically interesting DNA-protein complexes is very difficult, because higher resolution, atomistic models can only be applied to very small systems, while common coarse-grained models are often based on ad hoc assumptions. In our recent and on-going work, we have carried out atomistic simulations of nucleosomes and their various substructures, such as histone tails. The latter are positively charged, structurally disordered polyelectrolytes, which may interact with linker DNA as well as acidic patches on the nucleosomal histones. Our simulations revealed the conformational landscapes of free tails, and suggested how their specific post-translational modifications may control chromatin compaction. In related work, we have developed a rigorous, yet computationally efficient technique of deriving coarse-grained potentials for ions and biomolecules from corresponding atomistic simulations, based on matching partition functions between two scales. These coarse-grained models allows one to follow various physical properties and interactions between biomolecules, as environmental conditions are varied, such as the salt concentration. Finally, we have developed a new, general technique for computing a free energy difference between two conformations of a macromolecule, which we applied to study the transition of Adenylate Kinase, a 214-residue allosteric protein.

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