Jump to main content
Jump to site search

Issue 5, 2012
Previous Article Next Article

Mutational Locally Enhanced Sampling (MULES) for quantitative prediction of the effects of mutations at proteinprotein interfaces

Author affiliations

Abstract

We have successfully developed and validated with experiment a new computational method for quantitatively predicting the effects of mutations at a proteinprotein interface. From over 500 ns of explicitly solvated molecular dynamics, Mutational Locally Enhanced Sampling (MULES) shows significantly improved accuracy over post-processing methods for a prototypical set of mutations, with a maximum mean unsigned error to experiment of 0.5 kcal mol−1 and comparable or better precision. The technique in principle allows the effect of any mutation to be calculated, whether natural or non-natural. The versatility, quantitative accuracy, high precision and speed of MULES compared to existing computational prediction techniques enhance its potential for modelling changes to the interface in a systematic way, thereby aiding peptide and protein interaction design.

Graphical abstract: Mutational Locally Enhanced Sampling (MULES) for quantitative prediction of the effects of mutations at protein–protein interfaces

Back to tab navigation

Supplementary files

Publication details

The article was received on 08 Nov 2011, accepted on 15 Feb 2012 and first published on 24 Feb 2012


Article type: Edge Article
DOI: 10.1039/C2SC00895E
Citation: Chem. Sci., 2012,3, 1503-1511
  •   Request permissions

    Mutational Locally Enhanced Sampling (MULES) for quantitative prediction of the effects of mutations at proteinprotein interfaces

    R. T. Bradshaw, P. G. A. Aronica, E. W. Tate, R. J. Leatherbarrow and I. R. Gould, Chem. Sci., 2012, 3, 1503
    DOI: 10.1039/C2SC00895E

Search articles by author

Spotlight

Advertisements