hydrogen-bond driven loop-closure kinetics in unfolded polypeptide chains形成氢键驱动loop-closure动力学在展开的多肽链.pdfVIP

Hydrogen-Bond Driven Loop-Closure Kinetics in Unfolded Polypeptide Chains 1,2 3,4 ¨ 3 3 1,5 Isabella Daidone *, Hannes Neuweiler , Soren Doose , Markus Sauer , Jeremy C. Smith * 1 Interdisciplinary Center for Scientific Computing, University of Heidelberg, Heidelberg, Germany, 2 Dipartimento di Chimica, Ingegneria Chimica e Materiali, University of L’Aquila, Coppito, Italy, 3 Applied Laser Physics Laser Spectroscopy, University of Bielefeld, Bielefeld, Germany, 4 Medical Research Council Centre for Protein Engineering, Cambridge, United Kingdom, 5 University of Tennessee/Oak Ridge National Laboratory, Center for Molecular Biophysics, Oak Ridge, Tennessee, United States of America Abstract Characterization of the length dependence of end-to-end loop-closure kinetics in unfolded polypeptide chains provides an understanding of early steps in protein folding. Here, loop-closure in poly-glycine-serine peptides is investigated by combining single-molecule fluorescence spectroscopy with molecular dynamics simulation. For chains containing more than 10 peptide bonds loop-closing rate constants on the 20–100 nanosecond time range exhibit a power-law length dependence. However, this scaling breaks down for shorter peptides, which exhibit slower kinetics arising from a perturbation induced by the dye reporter system used in the experimental setup. The loop-closure kinetics in the longer peptides is found to be determined by the formation of intra-peptide hydrogen bonds and transient b-sheet structure, that accelerate the search for contacts among residues distant in sequence relative to the case of a polyp