title: 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 calculated 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 experiment, an analysis 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 determined. A covariance analysis 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.
authors: Department of Chemistry & Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors: Guobin
authors: G
authors: Luo
authors: Martin
authors: M
authors: Karplus
references: Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):11910-5
references: 16880391
references: Science. 2001 Mar 23;291(5512):2429-33
references: 11264542
references: Annu Rev Biochem. 1996;65:537-61
references: 8811189
references: J Phys Chem B. 2006 May 18;110(19):9363-7
references: 16686476
references: Science. 2003 Oct 10;302(5643):262-6
references: 14551431
references: Protein Sci. 2008 Aug;17(8):1295-307
references: 18560010
references: Biochemistry. 1999 Jun 1;38(22):7040-9
references: 10353815
references: Nature. 2007 Dec 6;450(7171):913-6
references: 18026087
references: Phys Rev Lett. 2004 Oct 29;93(18):180603
references: 15525146
references: J Phys Chem B. 2008 May 15;112(19):5988-96
references: 18266353
references: Nature. 2007 Dec 6;450(7171):838-44
references: 18026086
references: Science. 2001 Aug 24;293(5534):1395
references: 11520951
references: Proteins. 1991;11(3):205-17
references: 1749773
references: Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):893-8
references: 9927664