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Title: Molecular dynamics simulations of protein folding
Author: Pu, Mengchen
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2013
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Understanding protein folding is one of the most challenging problems remaining in molecular biology. Molecular dynamics (MD) simulation is an important technique, which is widely used for the investigation of biomolecular systems. Simplified models of protein folding and evolution have also been used to study protein folding mechanisms. Using MD simulations, several comparisons have been performed to study the behaviour of the Ph ox and Bern I p (PB I) domain. The PB I domain, which adopts an ubiquitin-like p-grasp fold, is an 86-residue interaction module conserved in many species. It participates in diverse biological processes. An accurate model of the protein's equilibrium dynamics is a prerequisite for fUliher investigations. Initial MD simulations with two different CHARMM force fields using implicit and explicit solvent models have been perfonned, focusing on the structural and dynamics properties of the protein. EEF 1.1 with the CHARMM 19 force field may less accurately reproduce the protein motion and folding pathways. Using a simplified approach coarse-grained Go model, unfolding simulations have been performed of the wild-type and 28 single-site mutants of the PB 1 domain. The computational values are compared with kinetic experiments. The folding manner of the PB I domain appears to be a pseudo two-state kinetic process proposed from the thermodynamics and kinetics experiments. The influences of the different size of the time step in coarse-grained MD simulations have been discussed in detail. Using a large time step can accelerate the unfolding simulation. Finally, all-atom high temperature unfolding simulations with explicit solvent have been performed
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available