Premium
Conformational ensembles and sampled energy landscapes: Analysis and comparison
Author(s) -
Cazals Frédéric,
Dreyfus Tom,
Mazauric Dorian,
Roth ChristineAndrea,
Robert Charles H.
Publication year - 2015
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.23913
Subject(s) - energy landscape , computer science , metric (unit) , energy (signal processing) , software , cluster analysis , theoretical computer science , algorithm , topology (electrical circuits) , statistical physics , mathematics , artificial intelligence , combinatorics , physics , operations management , statistics , economics , thermodynamics , programming language
We present novel algorithms and software addressing four core problems in computational structural biology, namely analyzing a conformational ensemble, comparing two conformational ensembles, analyzing a sampled energy landscape, and comparing two sampled energy landscapes. Using recent developments in computational topology, graph theory, and combinatorial optimization, we make two notable contributions. First, we present a generic algorithm analyzing height fields. We then use this algorithm to perform density‐based clustering of conformations, and to analyze a sampled energy landscape in terms of basins and transitions between them. In both cases, topological persistence is used to manage (geometric) frustration. Second, we introduce two algorithms to compare transition graphs. The first is the classical earth mover distance metric which depends only on local minimum energy configurations along with their statistical weights, while the second incorporates topological constraints inherent to conformational transitions. Illustrations are provided on a simplified protein model (BLN69), whose frustrated potential energy landscape has been thoroughly studied. The software implementing our tools is also made available, and should prove valuable wherever conformational ensembles and energy landscapes are used. © 2015 Wiley Periodicals, Inc.