Proteins are dynamic macromolecules that perform vital functions in cells. A protein structure determines its function, but this structure is not static, as proteins change their conformation to achieve various functions. Understanding the conformational landscapes of proteins is essential to understand their mechanism of action. Sets of carefully chosen conformations can summarize such complex landscapes and provide better insights into protein function than single conformations. We refer to these sets as representative conformational ensembles. Recent advances in computational methods have led to an increase in the number of available structural datasets spanning conformational landscapes. However, extracting representative conformational ensembles from such datasets is not an easy task and many methods have been developed to tackle it. Our new approach, EnGens (short for ensemble generation), collects these methods into a unified framework for generating and analyzing representative protein conformational ensembles. In this work, we: (1) provide an overview of existing methods and tools for representative protein structural ensemble generation and analysis; (2) unify existing approaches in an open-source Python package, and a portable Docker image, providing interactive visualizations within a Jupyter Notebook pipeline; (3) test our pipeline on a few canonical examples from the literature. Representative ensembles produced by EnGens can be used for many downstream tasks such as protein-ligand ensemble docking, Markov state modeling of protein dynamics and analysis of the effect of single-point mutations.

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.

Sampling-based motion planning algorithms from the field of robotics have been very successful in exploring the conformational space of proteins. However, studying the flexibility of large proteins with hundreds or thousands of Degrees of Freedom (DoFs) remains a big challenge. Large proteins are also highly-constrained systems, which makes them more challenging for standard robotic approaches. So-called "expansive" motion planning algorithms were specifically developed to address highly-dimensional and highly-constrained problems. Many such planners employ a low-dimensional projection to estimate exploration coverage and direct their search based on this information. We believe that such a projection plays an essential role in the success of these planners. This paper shows how the low-dimensional projection used by expansive planners can be tailored with respect to a given molecular system to enhance the process of conformational sampling. We introduce a methodology to generate an expert projection using any available information about a given protein. We evaluate this methodology on several conformational search problems involving proteins with hundreds of DoFs. Our experiments demonstrate that incorporating expert knowledge into the projection can significantly benefit the exploration process.

Obtaining 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.

The Transition-based RRT (T-RRT) is a variant of RRT developed for path planning on a continuous cost space, i.e. a configuration space featuring a continuous cost function. It has been used to solve complex, high-dimensional problems in robotics and structural biology. In this paper, we propose a multiple-tree variant of T-RRT, named Multi-T-RRT. It is especially useful to solve ordering-and-pathfinding problems, i.e. to compute a path going through several unordered way-points. Using the Multi-T-RRT, such problems can be solved from a purely geometrical perspective, without having to use a symbolic task planner. We evaluate the Multi-T-RRT on several path planning problems and compare it to other path planners. Finally, we apply the Multi-T-RRT to a concrete industrial inspection problem involving an aerial robot.

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.

This paper addresses the problem of parallelizing the Rapidly-exploring Random Tree (RRT) algorithm on large-scale distributed-memory architectures, using the message passing interface. We compare three parallel versions of RRT based on classical parallelization schemes. We evaluate them on different motion-planning problems and analyze the various factors influencing their performance.

This paper addresses the problem of improving the performance of the Rapidly-exploring Random Tree (RRT) algorithm by parallelizing it. For scalability reasons we do so on a distributed-memory architecture, using the message-passing paradigm. We present three parallel versions of RRT along with the technicalities involved in their implementation. We also evaluate the algorithms and study how they behave on different motion planning problems.

Jointly working on shared digital artifacts – such as wikis – is a well-tried method of developing knowledge collectively within a group or organization. Our assumption is that such knowledge maturing is an accommodation process that can be measured by taking the writing process itself into account. This paper describes the development of a tool that detects accommodation automatically with the help of machine learning algorithms. We applied a software framework for task detection to the automatic identification of accommodation processes within a wiki. To set up the learning algorithms and test its performance, we conducted an empirical study, in which participants had to contribute to a wiki and, at the same time, identify their own tasks. Two domain experts evaluated the participants’ micro-tasks with regard to accommodation. We then applied an ontology-based task detection approach that identified accommodation with a rate of 79.12%. The potential use of our tool for measuring knowledge maturing online is discussed.

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.