Journal of Chemical Information and Modeling
Journal of Chemical Information and Modeling
5 years ago

Characterizing Drug–Target Residence Time with Metadynamics: How To Achieve Dissociation Rate Efficiently without Losing Accuracy against Time-Consuming Approaches

Characterizing Drug–Target Residence Time with Metadynamics: How To Achieve Dissociation Rate Efficiently without Losing Accuracy against Time-Consuming Approaches
Mingyun Shen, Yu Kang, Dan Li, Youyong Li, Tingjun Hou, Huiyong Sun
Drug–target residence time plays a vital role in drug efficacy. However, there is still no effective strategy to predict drug residence time. Here, we propose to use the optimized (or minimized) structures derived from holo-state proteins to calculate drug residence time, which could give a comparable or even better prediction accuracy compared with those calculated utilizing a large number of molecular dynamics (MD) structures based on the Poisson process. Besides, in addition to the Poisson process, one may use fewer samples for predicting residence time due to the reason that, in a large extent, the calculated drug residence time is stable and independent of the number of samples used for the prediction. With remarkably reduced computational load, the proposed strategy may be promising for large-scale drug residence time prediction, such as post-processing in virtual screening (VS) and lead compound optimization.

Publisher URL: http://dx.doi.org/10.1021/acs.jcim.7b00075

DOI: 10.1021/acs.jcim.7b00075

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.