Theoretical studies of unfolding and hydration of protein ions in the gas phase and a charge-induced phase transition in polymers.

摘要

Motivated by ion mobility studies, molecular dynamics simulations have been carried out to study the unfolding, refolding and hydration of unsolvated protein ions. The temperature-induced unfolding simulations have been performed on the +5 and +7 charge states at 300K and at 600K, and charge-induced unfolding was examined in the protonated charge states +3 to +19 at 300K. The simulations reproduce the main features of experimental data, and provide physical insight into how the energy landscape changes with charge, into the key step in unfolding structural changes and into the nature of the unfolded conformations of the higher charge states.; Simulations have been used to investigate the initial stage in the hydration of unsolvated ions. An internal hydration site in the BPTI ion is found to be associated with the large entropy change of water binding, as a result of tetrahedral coordination of a water molecule with the protein atoms. It is energetically more favorable to hydrate the compact cytochrome c conformation than the unfolded conformation at the initial stage of hydration, due to better satisfaction of multiple hydrogen bond interactions between water and protein atoms in the compact conformation. These results provide physical explanations for the experimental observations.; To generalize the compact-to-extended conformational change induced by charge in macromolecules, analytical mean-field theories are developed to study the nature of this transition. The compact-to-extended transition induced by charge is found to be first-order in the presence of strong short-range interactions at low temperatures, and second-order if the short-range interactions are weak. The prediction is compared to the computer simulation of the exhaustive enumeration of all 12-mer cubic lattice polymer conformations using different potentials, and qualitative agreement is found. Implications for protein folding are discussed.