The effect of environment on peptide and protein folding: a molecular dynamics study

The focus of the PhD has been the investigation of the environmental effects on peptide and protein folding. Specifically molecular dynamics (MD) simulations using explicit water have been performed to analyze in detail specific conditions that either promote or inhibit protein folding. The initial work focused on the ability of the force field to reproduce the folding dynamics of a series of small peptides in water. It was found that the conformational properties were well reproduced but the folding times derived from the simulations were considerably shorter than that estimated from experiment. It is part of this work a new set of dihedral potentials was also derived that gave a better agreement between the simulations and the available X-ray data. An approach was also investigated in detail, which attempts to mimic the effect of the chaperon GroEL by modifying the polarity of the solvent environment. Within cells, chaperons such as GroEL facilitate the folding of protein and peptides in an energy dependant manner. The simulations showed that mimicking the effect of the chaperon could facilitate the rate of folding of small peptides as well as a small protein from thermally denatured states. Finally the effect of interfaces on peptide folding was investigated, looking at the effect of polyethylene glycol (PEG) spacers on the conformational properties of small peptides and the interfacial structure of self-assembled switchable peptide surfactants.