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Gewählte Master / Diploma Thesis:

Jan Walther Perthold (2017): CALCULATION OF PROTEIN-PROTEIN BINDING FREE ENERGIES USING MOLECULAR DYNAMICS SIMULATIONS.
Master / Diploma Thesis - Institut für Molekulare Modellierung und Simulation (MMS), BOKU-Universität für Bodenkultur, pp 96. UB BOKU obvsg

Data Source: ZID Abstracts
Abstract:
Virtually all biological processes depend on the interaction between proteins at some point. The correct prediction of biomolecular binding free-energies has many interesting applications in both basic and applied pharmaceutical research. While recent advances in the field of molecular dynamics (MD) simulations have proven the feasibility of the calculation of protein-protein binding free energies, the large conformational freedom of proteins and complex free energy landscapes of binding reactions make such calculations a difficult task. Moreover, convergence and reversibility of resulting free-energy values remain poorly described. In this work, a relatively simple methodology for the calculation of standard-state protein-protein binding free energies using hidden distance restraints is discussed and evaluated by practical application to a small model complex of Ubiquitin and the Ubiquitin-binding domain of human DNA Polymerase ι (UBM2). All computed free energy differences were closely monitored for convergence. While in principle the computed binding free-energies are also influenced by the used force-field, the calculated binding free energies of UBM2 and Ubiquitin were in very good agreement with experimental values and error estimates were in the order of thermal noise. However, free-energy calculations involving a mutant UBM2 domain did not converge within the given simulation time. Furthermore, simulation results suggest that the applicability of the presented method to small and very flexible proteins and to biomolecular complexes with less favorable binding free energies might be limited. The presented method remains to be evaluated further and possibilities for improvement remain to be tested.

Beurteilende(r): Oostenbrink Chris
1.Mitwirkender: Pechlaner Maria

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