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Review
. 2011 Feb;21(1):4-11.
doi: 10.1016/j.sbi.2010.10.006.

Taming the complexity of protein folding

Gregory R Bowman  1 , Vincent A Voelz, Vijay S Pande
Affiliations
Review

Taming the complexity of protein folding

Gregory R Bowman et al. Curr Opin Struct Biol. 2011 Feb.

Abstract

Protein folding is an important problem in structural biology with significant medical implications, particularly for misfolding disorders like Alzheimer's disease. Solving the folding problem will ultimately require a combination of theory and experiment, with theoretical models providing a comprehensive view of folding and experiments grounding these models in reality. Here we review progress towards this goal over the past decade, with an emphasis on recent theoretical advances that are empowering chemically detailed models of folding and the new results these technologies are providing. In particular, we discuss new insights made possible by Markov state models (MSMs), including the role of non-native contacts and the hub-like character of protein folded states.

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Figures

Figure 1
Figure 1
The average folding time versus length for a number of fast-folding proteins from the experimental literature that are candidates for atomistic simulations and MSMs. Overlays of the crystal structure (cyan) and our predicted native state (dark blue) are shown for a number of systems highlighted in this review.
Figure 2
Figure 2
The highest flux folding pathways from a 2000-state MSM for NTL9 taken from Ref [18]. These pathways account for only ~25% of the total flux and transit only 14 of the 2000 metastable states (labeled a-n). The size of each state is proportional to the logarithm of its equilibrium population and arrow sizes are proportional to the logarithm of the interstate flux.
Figure 3
Figure 3
Schematic of a native hub model with a native state (N) and non-native states (nn) taken from Ref [20]. The size of each node is correlated with its equilibrium probability and the connectivity falls off as one moves away from the native state.
See this image and copyright information in PMC

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