IGLOO: An Iterative Global Exploration and Local Optimization Algorithm to Find Diverse Low-Energy Conformations of Flexible Molecules

William Margerit (1) , Antoine Charpentier (1) , Cathy Maugis-Rabusseau (2, 3) , Johann Christian Schön (4) , Nathalie Tarrat (5) , Juan Cortés (1)

1 LAAS-RIS - Équipe Robotique et InteractionS
2 IMT - Institut de Mathématiques de Toulouse UMR5219
3 INSA Toulouse - Institut National des Sciences Appliquées - Toulouse
4 Max Planck Institute for Solid State Research
5 CEMES-SINanO - Surfaces, Interfaces et Nano-Objets

The exploration of the energy landscape of a chemical system is essential for understanding and predicting its observable properties. In most cases, this is a challenging task due to the high complexity of such landscapes, which often consist of multiple, possibly hierarchical basins that are difficult to locate and thoroughly explore. In this study, we introduce a novel method, called IGLOO (Iterative Global Exploration and Local Optimization), which aims to achieve a more efficient global exploration of the conformational space compared to existing techniques. The method utilizes a tree-based exploration inspired by the Rapidly exploring Random Tree (RRT) algorithm originating from robotics. IGLOO dynamically adjusts its exploration strategy to both homogeneously scan the landscape and focus on promising regions, avoiding redundant exploration. We evaluated IGLOO using models of two polypeptides and compared its performance to the traditional basin-hopping method and a hybrid method that also incorporates the RRT algorithm. We find that IGLOO outperforms both alternative methods in terms of efficiently and comprehensively exploring the molecular conformational space. This approach can be easily generalized to other chemical systems such as molecules on surfaces or crystalline systems.

Keywords: global optimization stochastic sampling algorithms global energy landscape exploration flexible molecules polypeptides; global optimization; stochastic sampling algorithms; global energy landscape exploration; flexible molecules; polypeptides

Domains: Modeling and Simulation; Theoretical and/or physical chemistry; Bioinformatics [q-bio.QM]; Robotics [cs.RO]; Optimization and Control [math.OC]; Quantum Physics [quant-ph]

William Margerit, Antoine Charpentier, Cathy Maugis-Rabusseau, Johann Christian Schön, Nathalie Tarrat, et al.. IGLOO: An Iterative Global Exploration and Local Optimization Algorithm to Find Diverse Low-Energy Conformations of Flexible Molecules. Algorithms, 2023, 16 (10), pp.476. ⟨10.3390/a16100476⟩. ⟨hal-04247201⟩