To milliseconds and beyond: Challenges in the simulation of protein folding

Thomas J. Lane, Diwakar Shukla, Kyle A. Beauchamp, Vijay S. Pande

Research output: Contribution to journalReview articlepeer-review

Abstract

Quantitatively accurate all-atom molecular dynamics (MD) simulations of protein folding have long been considered a holy grail of computational biology. Due to the large system sizes and long timescales involved, such a pursuit was for many years computationally intractable. Further, sufficiently accurate forcefields needed to be developed in order to realistically model folding. This decade, however, saw the first reports of folding simulations describing kinetics on the order of milliseconds, placing many proteins firmly within reach of these methods. Progress in sampling and forcefield accuracy, however, presents a new challenge: how to turn huge MD datasets into scientific understanding. Here, we review recent progress in MD simulation techniques and show how the vast datasets generated by such techniques present new challenges for analysis. We critically discuss the state of the art, including reaction coordinate and Markov state model (MSM) methods, and provide a perspective for the future.

Original languageEnglish (US)
Pages (from-to)58-65
Number of pages8
JournalCurrent Opinion in Structural Biology
Volume23
Issue number1
DOIs
StatePublished - Feb 2013
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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