Sampling-based algorithms for path planning, such as the Rapidly-exploring Random Tree (RRT), have achieved great success, thanks to their ability to efficiently solve complex high-dimensional problems. However, standard versions of these algorithms cannot guarantee optimality or even high-quality for the produced paths. In recent years, variants of these methods, such as T-RRT, have been proposed to deal with cost spaces: by taking configuration-cost functions into account during the exploration process, they can produce high-quality (i.e., low-cost) paths. Other novel variants, such as RRT*, can deal with optimal path planning: they ensure convergence toward the optimal path, with respect to a given path-quality criterion. In this paper, we propose to solve a complex problem encompassing this two paradigms: optimal path planning in a cost space. For that, we develop two efficient sampling-based approaches that combine the underlying principles of RRT* and T-RRT. These algorithms, called T-RRT* and AT-RRT, offer the same asymptotic optimality guarantees as RRT*. Results presented on several classes of problems show that they converge faster than RRT* toward the optimal path, especially when the topology of the search space is complex and/or when its dimensionality is high.

Understanding the challenges of protein flexibility in drug design. . ???aop.label???. doi: 10.1517/17460441.2015.1094458

Molecular docking is a standard computational approach to predict binding modes of protein–ligand complexes by exploring alternative orientations and conformations of the ligand (i.e., by exploring ligand flexibility). Docking tools are largely used for virtual screening of small drug-like molecules, but their accuracy and efficiency greatly decays for ligands with more than 10 flexible bonds. This prevents a broader use of these tools to dock larger ligands, such as peptides, which are molecules of growing interest in cancer research. To overcome this limitation, our group has previously proposed a meta-docking strategy, called DINC, to predict binding modes of large ligands. By incrementally docking overlapping fragments of a ligand, DINC allowed predicting binding modes of peptide-based inhibitors of transcription factors involved in cancer. Here, we describe DINC 2.0, a revamped version of the DINC webserver with enhanced capabilities and a more user-friendly interface. DINC 2.0 allows docking ligands that were previously too challenging for DINC, such as peptides with more than 25 flexible bonds. The webserver is freely accessible at http://dinc.kavrakilab.org, together with additional documentation and video tutorials. Our team will provide continuous support for this tool and is working on extending its applicability to other challenging fields, such as personalized immunotherapy against cancer. Cancer Res; 77(21); e55–57. ©2017 AACR.

Understanding the mechanisms involved in the activation of an immune response is essential to many fields in human health, including vaccine development and personalized cancer immunotherapy. A central step in the activation of the adaptive immune response is the recognition, by T-cell lymphocytes, of peptides displayed by a special type of receptor known as Major Histocompatibility Complex (MHC). Considering the key role of MHC receptors in T-cell activation, the computational prediction of peptide binding to MHC has been an important goal for many immunological applications. Sequence- based methods have become the gold standard for peptide-MHC binding affinity prediction, but structure-based methods are expected to provide more general predictions (i.e., predictions applicable to all types of MHC receptors). In addition, structural modeling of peptide-MHC complexes has the potential to uncover yet unknown drivers of T-cell activation, thus allowing for the development of better and safer therapies. In this review, we discuss the use of computational methods for the structural modeling of peptide-MHC complexes (i.e., binding mode prediction) and for the structure-based prediction of binding affinity.

The Transition-based RRT (T-RRT) algorithm enables to solve motion planning problems involving configuration spaces over which cost functions are defined, or cost spaces for short. T-RRT has been successfully applied to diverse problems in robotics and structural biology. In this paper, we aim at enhancing T-RRT to solve ever more difficult problems involving larger and more complex cost spaces. We compare several variants of T-RRT by evaluating them on various motion planning problems involving different types of cost functions and different levels of geometrical complexity. First, we explain why applying as such classical extensions of RRT to T-RRT is not helpful, both in a mono-directional and in a bidirectional context. Then, we propose an efficient Bidirectional T-RRT, based on a bidirectional scheme tailored to cost spaces. Finally, we illustrate the new possibilities offered by the Bidirectional T-RRT on an industrial inspection problem.

We present an individual-based predator-prey model with, for the first time, each agent behavior being modeled by a fuzzy cognitive map (FCM), allowing the evolution of the agent behavior through the epochs of the simulation. The FCM enables the agent to evaluate its environment (e.g., distance to predator or prey, distance to potential breeding partner, distance to food, energy level) and its internal states (e.g., fear, hunger, curiosity), and to choose several possible actions such as evasion, eating, or breeding. The FCM of each individual is unique and is the result of the evolutionary process. The notion of species is also implemented in such a way that species emerge from the evolving population of agents. To our knowledge, our system is the only one that allows the modeling of links between behavior patterns and speciation. The simulation produces a lot of data, including number of individuals, level of energy by individual, choice of action, age of the individuals, and average FCM associated with each species. This study investigates patterns of macroevolutionary processes, such as the emergence of species in a simulated ecosystem, and proposes a general framework for the study of specific ecological problems such as invasive species and species diversity patterns. We present promising results showing coherent behaviors of the whole simulation with the emergence of strong correlation patterns also observed in existing ecosystems.