Molecular Simulations of Accelerated Protein Folding

In this thesis, molecular dynamics (MD) simulations were employed to investigate the effects of electric fields on the dynamic processes of proteins, including protein folding, hydration, and agglomeration dynamics. By comparing the simulation results with and without external electric fields, the influence of electric fields on folding pathways of a mini protein named chignolin, free-energy landscapes, state transitions, and hydrogenbond dynamics were explored. For larger proteins like eotaxin and prion, an enhancedsampling methodology referred to as ratchet-and-pawl molecular dynamics (rpMD) was utilized to facilitate protein folding of larger proteins, specifically eotaxin and prion, within a computationally feasible simulation timescale. The current investigation also encompassed an examination of the hydration dynamics of Hen Egg White Lysozyme (HEWL) in the presence of external electric fields, wherein the dipolar response of water molecules on the protein surface was scrutinized. The outcomes thereof yielded discernment into the rotational response of water molecules in the hydration layer, along with the impact from the protein surface, under varying frequencies and intensities of electric fields. In addition, the agglomeration formation process of chignolin and prion was investigated, revealing that effective agglomeration is predominantly driven by the intricate interplay of multiple residues interactions
within larger protein structures.