4 years ago

Accelerating physical simulations of proteins by leveraging external knowledge

Accelerating physical simulations of proteins by leveraging external knowledge
Ken A. Dill, Joseph A. Morrone, Alberto Perez
It is challenging to compute structure-function relationships of proteins using molecular physics. The problem arises from the exponential scaling of the computational searching and sampling of large conformational spaces. This scaling challenge is not met by today's methods, such as Monte Carlo, simulated annealing, genetic algorithms, or molecular dynamics (MD) or its variants such as replica exchange. Such methods of searching for optimal states on complex probabilistic landscapes are referred to more broadly as Explore-and-Exploit (EE), including in contexts such as computational learning, games, industrial planning, and modeling military strategies. Here, we describe a Bayesian method, called MELD, that ‘melds’ together EE approaches with externally added information that can be vague, combinatoric, noisy, intuitive, heuristic, or from experimental data. MELD is shown to accelerate physical MD simulations when using experimental data to determine protein structures; for predicting protein structures by using heuristic directives; and when predicting binding affinities of proteins from limited information about the binding site. Such Guided EE approaches might also be useful beyond proteins and beyond molecular science. For further resources related to this article, please visit the WIREs website. Board games such as chess and Go have been computational grand challenges because of the large number of options to explore. Computer successes in defeating human grand masters were not just because of raw hardware power, but also due to clever heuristics. Folding proteins requires surmounting even bigger computational search problems, even though nature finds those states through physics rapidly, usually within seconds. A broad range of STEM problems could benefit from combining physics with new heuristics approaches.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/wcms.1309

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.