title: Conformational ensembles and sampled energy landscapes: Analysis and comparison.
abstract: 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.
authors.affiliation: Inria 2004 route des Lucioles, BP 93, F-06902 Sophia-Antipolis, FRANCE.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Cazals
authors.affiliation: Inria 2004 route des Lucioles, BP 93, F-06902 Sophia-Antipolis, FRANCE.
authors.forename: Tom
authors.initials: T
authors.lastname: Dreyfus
authors.affiliation: Inria 2004 route des Lucioles, BP 93, F-06902 Sophia-Antipolis, FRANCE.
authors.forename: Dorian
authors.initials: D
authors.lastname: Mazauric
authors.affiliation: Inria 2004 route des Lucioles, BP 93, F-06902 Sophia-Antipolis, FRANCE.
authors.forename: Christine-Andrea
authors.initials: CA
authors.lastname: Roth
authors.affiliation: CNRS Laboratory of Theoretical Biochemistry (LBT) Institut de Biologie Physico-Chimique 13, rue Pierre et Marie Curie 75005 Paris.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Robert
mesh_terms: D000465:Algorithms; D008958:Models, Molecular; D008968:Molecular Conformation; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012984:Software; D013816:Thermodynamics
chemical_list: D011506:Proteins
keywords: Morse theory; energy landscapes; molecular conformations; optimal transport; optimization; sampling