Sampling-based methods for a full characterization of energy landscapes of small peptides

International audienceObtaining accurate representations of energy landscapes of biomolecules such as proteins and peptides is central to structure-function studies. Peptides are particularly interesting, as they exploit structural flexibility to modulate their biological function. Despite their small size, peptide modeling remains challenging due to the complexity of the energy landscape of such highly-flexible dynamic systems. Currently, only sampling-based methods can efficiently explore the conformational space of a peptide. In this paper, we suggest to combine two such methods to obtain a full characterization of energy landscapes of small yet flexible peptides. First, we propose a simplified version of the classical Basin Hopping algorithm to quickly reveal the meta-stable structural states of a peptide and the corresponding low-energy basins in the landscape. Then, we present several variants of a robotics-inspired algorithm, the Transition-based Rapidly-exploring Random Tree, to quickly determine transition state and transition path ensembles, as well as transition probabilities between meta-stable states. We demonstrate this combined approach on the terminally-blocked alanine

Extensions of sampling-based approaches to path planning in complex cost spaces: applications to robotics and structural biology

Planifier le chemin d’un robot dans un environnement complexe est un problème crucial en robotique. Les méthodes de planification probabilistes peuvent résoudre des problèmes complexes aussi bien en robotique, qu’en animation graphique, ou en biologie structurale. En général, ces méthodes produisent un chemin évitant les collisions, sans considérer sa qualité. Récemment, de nouvelles approches ont été créées pour générer des chemins de bonne qualité : en robotique, cela peut être le chemin le plus court ou qui maximise la sécurité ; en biologie, il s’agit du mouvement minimisant la variation énergétique moléculaire. Dans cette thèse, nous proposons plusieurs extensions de ces méthodes, pour améliorer leurs performances et leur permettre de résoudre des problèmes toujours plus difficiles. Les applications que nous présentons viennent de la robotique (inspection industrielle et manipulation aérienne) et de la biologie structurale (mouvement moléculaire et conformations stables). ABSTRACT : Planning a path for a robot in a complex environment is a crucial issue in robotics. So-called probabilistic algorithms for path planning are very successful at solving difficult problems and are applied in various domains, such as aerospace, computer animation, and structural biology. However, these methods have traditionally focused on finding paths avoiding collisions, without considering the quality of these paths. In recent years, new approaches have been developed to generate high-quality paths: in robotics, this can mean finding paths maximizing safety or control; in biology, this means finding motions minimizing the energy variation of a molecule. In this thesis, we propose several extensions of these methods to improve their performance and allow them to solve ever more difficult problems. The applications we present stem from robotics (industrial inspection and aerial manipulation) and structural biology (simulation of molecular motions and exploration of energy landscapes)