2mwf | pdb_00002mwf
NMR structure of FBP28 WW2 mutant Y438R DN
Structural highlights
Function[TCRG1_HUMAN] Transcription factor that binds RNA polymerase II and inhibits the elongation of transcripts from target promoters. Regulates transcription elongation in a TATA box-dependent manner. Necessary for TAT-dependent activation of the human immunodeficiency virus type 1 (HIV-1) promoter.[1] [2] Publication Abstract from PubMedTo demonstrate the utility of the coarse-grained united-residue (UNRES) force field to compare experimental and computed kinetic data for folding proteins, we have performed long-time millisecond-timescale canonical Langevin molecular dynamics simulations of the triple beta-strand from the Formin binding protein 28 WW domain and six nonnatural variants, using UNRES. The results have been compared with available experimental data in both a qualitative and a quantitative manner. Complexities of the folding pathways, which cannot be determined experimentally, were revealed. The folding mechanisms obtained from the simulated folding kinetics are in agreement with experimental results, with a few discrepancies for which we have accounted. The origins of single- and double-exponential kinetics and their correlations with two- and three-state folding scenarios are shown to be related to the relative barrier heights between the various states. The rate constants obtained from time profiles of the fractions of the native, intermediate, and unfolded structures, and the kinetic equations fitted to them, correlate with the experimental values; however, they are about three orders of magnitude larger than the experimental ones for most of the systems. These differences are in agreement with the timescale extension derived by scaling down the friction of water and averaging out the fast degrees of freedom when passing from all-atom to a coarse-grained representation. Our results indicate that the UNRES force field can provide accurate predictions of folding kinetics of these WW domains, often used as models for the study of the mechanisms of proein folding. Folding kinetics of WW domains with the united residue force field for bridging microscopic motions and experimental measurements.,Zhou R, Maisuradze GG, Sunol D, Todorovski T, Macias MJ, Xiao Y, Scheraga HA, Czaplewski C, Liwo A Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):18243-8. doi:, 10.1073/pnas.1420914111. Epub 2014 Dec 8. PMID:25489078[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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