Combining Experiments and Simulations Using the Maximum Entropy Principle

Wouter Boomsma, Jesper Ferkinghoff-Borg, Kresten Lindorff-Larsen

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    Abstract

    A key component of computational biology is to compare the results of computer modelling with experimental measurements. Despite substantial progress in the models and algorithms used in many areas of computational biology, such comparisons sometimes reveal that the computations are not in quantitative agreement with experimental data. The principle of maximum entropy is a general procedure for constructing probability distributions in the light of new data, making it a natural tool in cases when an initial model provides results that are at odds with experiments. The number of maximum entropy applications in our field has grown steadily in recent years, in areas as diverse as sequence analysis, structural modelling, and neurobiology. In this Perspectives article, we give a broad introduction to the method, in an attempt to encourage its further adoption. The general procedure is explained in the context of a simple example, after which we proceed with a real-world application in the field of molecular simulations, where the maximum entropy procedure has recently provided new insight. Given the limited accuracy of force fields, macromolecular simulations sometimes produce results that are at not in complete and quantitative accordance with experiments. A common solution to this problem is to explicitly ensure agreement between the two by perturbing the potential energy function towards the experimental data. So far, a general consensus for how such perturbations should be implemented has been lacking. Three very recent papers have explored this problem using the maximum entropy approach, providing both new theoretical and practical insights to the problem. We highlight each of these contributions in turn and conclude with a discussion on remaining challenges.
    Original languageEnglish
    Article numbere1003406
    JournalP L o S Computational Biology (Online)
    Volume10
    Issue number2
    Number of pages9
    ISSN1553-7358
    DOIs
    Publication statusPublished - 2014

    Bibliographical note

    This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    Keywords

    • BIOCHEMICAL
    • MATHEMATICAL
    • MOLECULAR-DYNAMICS SIMULATIONS
    • INFERENTIAL STRUCTURE DETERMINATION
    • ENSEMBLE REFINEMENT
    • PROTEIN-STRUCTURE
    • ENERGY FUNCTION
    • MODELS
    • STATE
    • NMR
    • RECONSTRUCTION
    • POLYPEPTIDES

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