Effects of mutation, truncation, and temperature on the folding kinetics of a WW domain.

Journal of Molecular Biology
Gia G MaisuradzeHarold A Scheraga

Abstract

The purpose of this work is to show how mutation, truncation, and change of temperature can influence the folding kinetics of a protein. This is accomplished by principal component analysis of molecular-dynamics-generated folding trajectories of the triple β-strand WW domain from formin binding protein 28 (FBP28) (Protein Data Bank ID: 1E0L) and its full-size, and singly- and doubly-truncated mutants at temperatures below and very close to the melting point. The reasons for biphasic folding kinetics [i.e., coexistence of slow (three-state) and fast (two-state) phases], including the involvement of a solvent-exposed hydrophobic cluster and another delocalized hydrophobic core in the folding kinetics, are discussed. New folding pathways are identified in free-energy landscapes determined in terms of principal components for full-size mutants. Three-state folding is found to be a main mechanism for folding the FBP28 WW domain and most of the full-size and truncated mutants. The results from the theoretical analysis are compared to those from experiment. Agreements and discrepancies between the theoretical and experimental results are discussed. Because of its importance in understanding protein kinetics and function, the diffusive...Continue Reading

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Citations

Jul 16, 2014·Journal of Molecular Modeling·Adam LiwoBartłomiej Zaborowski
Oct 21, 2015·Proceedings of the National Academy of Sciences of the United States of America·Gia G MaisuradzeHarold A Scheraga
Dec 10, 2014·Proceedings of the National Academy of Sciences of the United States of America·Rui ZhouAdam Liwo
May 20, 2015·Computational and Structural Biotechnology Journal·Nivedita Rai, Amutha Ramaswamy
Feb 18, 2016·Journal of Molecular Biology·Kapil DaveMartin Gruebele
May 18, 2016·The Journal of Chemical Physics·Agnieszka G LipskaHarold A Scheraga
Aug 6, 2013·Journal of Chemical Theory and Computation·Gia G MaisuradzeHarold A Scheraga
Nov 5, 2016·The Journal of Physical Chemistry. B·Khatuna KachlishviliGia G Maisuradze
Apr 10, 2020·The Journal of Physical Chemistry. B·Khatuna KachlishviliGia G Maisuradze

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