Protein engineering study of protein L by simulation

Journal of Computational Biology : a Journal of Computational Molecular Cell Biology
J M Sorenson, T Head-Gordon

Abstract

We examine the ability of our recently introduced minimalist protein model to reproduce experimentally measured thermodynamic and kinetic changes upon sequence mutation in the well-studied immunoglobulin-binding protein L. We have examined five different sequence mutations of protein L that are meant to mimic the same mutation type studied experimentally: two different mutations which disrupt the natural preference in the beta-hairpin #1 and beta-hairpin #2 turn regions, two different helix mutants where a surface polar residue in the alpha-helix has been mutated to a hydrophobic residue, and a final mutant to further probe the role of nonnative hydrophobic interactions in the folding process. These simulated mutations are analyzed in terms of various kinetic and thermodynamic changes with respect to wild type, but in addition we evaluate the structure-activity relationship of our model protein based on the phi-value calculated from both the kinetic and thermodynamic perspectives. We find that the simulated thermodynamic phi-values reproduce the experimental trends in the mutations studied and allow us to circumvent the difficult interpretation of the complicated kinetics of our model. Furthermore, the level of resolution of th...Continue Reading

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Citations

Jul 30, 2003·Biophysical Journal·Kresten Lindorff-LarsenMichele Vendruscolo
May 3, 2003·Current Opinion in Structural Biology·Teresa Head-Gordon, Scott Brown
Aug 17, 2010·Quarterly Reviews of Biophysics·Valentina Tozzini
Jul 13, 2005·The Journal of Chemical Physics·Serdal KirmizialtinDmitrii E Makarov
Jan 6, 2006·The Journal of Chemical Physics·Lei HuangDmitrii E Makarov
Jun 3, 2010·The Journal of Chemical Physics·Alex J Sodt, Teresa Head-Gordon
Oct 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Payel DasCecilia Clementi
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Scott BrownTeresa Head-Gordon
Jun 25, 2004·Protein Science : a Publication of the Protein Society·Cecilia Clementi, Steven S Plotkin
Sep 20, 2007·Proteins·Eng-Hui YapTeresa Head-Gordon
Oct 24, 2006·Biophysical Chemistry·Troy CellmerHarvey Blanch
Oct 31, 2006·Journal of Molecular Biology·Nicolas Lux FawziTeresa Head-Gordon
Nov 23, 2007·Biophysical Journal·Nicolas Lux FawziTeresa Head-Gordon
Nov 3, 2016·The Journal of Physical Chemistry. B·Sukanya SasmalTeresa Head-Gordon
Jan 31, 2008·Proceedings of the National Academy of Sciences of the United States of America·Erik D Nelson, Nick V Grishin
Dec 1, 2006·Biotechnology and Bioengineering·Dusan BratkoHarvey W Blanch
Feb 3, 2012·Journal of Computational Chemistry·Olga BezkorovaynayaChristine Peter
Mar 23, 2017·Scientific Reports·Stanislav M AvdoshenkoDmitrii E Makarov
Nov 13, 2004·Biotechnology and Bioengineering·Troy CellmerHarvey Blanch

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