Folding free energy surfaces of three small proteins under crowding: validation of the postprocessing method by direct simulation

摘要

We have developed a “postprocessing” method for modeling biochemical processes such as protein folding under crowded conditions. In contrast to the direct simulation approach, in which the protein undergoing folding is simulated along with crowders, the postprocessing method requires only the folding simulation without crowders. The influence of the crowders is then obtained by taking conformations from the crowder-free simulation and calculating the free energies of transferring to the crowders. This postprocessing yields the folding free energy surface of protein under crowding. Here the postprocessing results for the folding of three small proteins under “repulsive” crowding are validated by those obtained previously by the direct simulation approach. This validation confirms the accuracy of the postprocessing approach and highlights its distinct advantages in modeling biochemical processes under cell-like crowded conditions, such as enabling an atomistic representation of the test proteins.