Determining the Conformational Change that Accompanies Donor-​Acceptor Distance Fluctuations: An Umbrella Sampling Analysis

Abstract:

The response of a protein to variation of a specific coordinate can provide insights into the role of the overall architecture in the structural change. Given that the calcd. potential of mean force governing the fluctuation of an electron transfer donor-​acceptor distance in the NAD(P)​H:flavin oxidoreductase (Fre)​/FAD complex was shown to agree with expt., an anal. of the structural response of the rest of the protein to that distance change was made. Significant displacements are found throughout much of the protein, and the coupling pathway resulting in the structural changes was detd. A covariance anal. based on the quasiharmonic modes of the unperturbed protein was used to provide information concerning how the residue motions are correlated. It is found that of the three regions identified as moving together in an NMR study, two undergo significant structural changes when the electron donor-​acceptor distance is varied, and the third does not.