Conformational Substates of Wild Type and Mutant (V68N) Myoglobin-CO

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Shams, Hengameh | 2010

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Type of Document: M.Sc. Thesis
Language: Farsi
Document No: 40646 (04)
University: Sharif University of Technology
Department: Physics
Advisor(s): Ejtehadi, Mohammad Reza
Abstract:
Folded protein experience several conformational substates. Each substate reperesents a minimum in the free energy surface of the system. Since Myoglobin is the smallest protein that can reversibly bind to gas molecules and, it can be used as prototype for more complex systems.IR pecrtum of CO inside of myolgobin shows that distinct conformational substates can occur. It was shown that Histidine residue inside heme pocket plays an essential rolle in structural properties of substates. In this study, we used molecular dynamice simulation together with umbrella sampling method to obtain free energy profile of MbCO system. The configuration of distal Histidine (His64), CO and Heme is studied around free energy minima. The first dihedral of His64 makes the imidazole ring rotate and move away from the ligand. Mutation on Valin 68 causeds the stability of the Minimum converts to two smaller, Isoenergetic minima.This mutation decreases the energy barrier between A_1 and A_3 about kcal/mol. –value analysis shows that the intermediate and one of the transition states in wild type myoglobin differs from V68N mutant, due to different transition pathway, protein experiances.
Keywords:
Proteins ; Histidine ; Umbrella Sampling ; Mutant ; Folded ; Mayoglobin

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