TITLE

Analysis of the Free-Energy Surface of Proteins from Reversible Folding Simulations

AUTHOR(S)
Allen, Lucy R.; Krivov, Sergei V.; Paci, Emanuele
PUB. DATE
July 2009
SOURCE
PLoS Computational Biology;Jul2009, Vol. 5 Issue 7, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Computer generated trajectories can, in principle, reveal the folding pathways of a protein at atomic resolution and possibly suggest general and simple rules for predicting the folded structure of a given sequence. While such reversible folding trajectories can only be determined ab initio using all-atom transferable force-fields for a few small proteins, they can be determined for a large number of proteins using coarse-grained and structure-based force-fields, in which a known folded structure is by construction the absolute energy and free-energy minimum. Here we use a model of the fast folding helical λ-repressor protein to generate trajectories in which native and non-native states are in equilibrium and transitions are accurately sampled. Yet, representation of the free-energy surface, which underlies the thermodynamic and dynamic properties of the protein model, from such a trajectory remains a challenge. Projections over one or a small number of arbitrarily chosen progress variables often hide the most important features of such surfaces. The results unequivocally show that an unprojected representation of the free-energy surface provides important and unbiased information and allows a simple and meaningful description of many-dimensional, heterogeneous trajectories, providing new insight into the possible mechanisms of fast-folding proteins.
ACCESSION #
46792754

 

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