150 research outputs found
MoMA-LigPath: A web server to simulate protein-ligand unbinding
Protein-ligand interactions taking place far away from the active site, during ligand binding or release, may determine molecular specificity and activity. However, obtaining information about these interactions with experimental or computational methods remains difficult. The computational tool presented in this paper, MoMA-LigPath, is based on a mechanistic representation of the molecular system, considering partial flexibility, and on the application of a robotics-inspired algorithm to explore the conformational space. Such a purely geometric approach, together with the efficiency of the exploration algorithm, enables the simulation of ligand unbinding within very short computing time. Ligand unbinding pathways generated by MoMA-LigPath are a first approximation that can provide very useful information about protein-ligand interactions. When needed, this approximation can be subsequently refined and analyzed using state-of-the-art energy models and molecular modeling methods. MoMA-LigPath is available at http://moma.laas.fr. The web server is free and open to all users, with no login requirement
Parallelizing RRT on distributed-memory architectures
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
Algorithmes pour le (dés)assemblage d'objets complexes et applications à la biologie structurale
La compréhension et la prédiction des relations structure-fonction de protéines par des approches in sillico représentent aujourd'hui un challenge. Malgré le développement récent de méthodes algorithmiques pour l'étude du mouvement et des interactions moléculaires, la flexibilité de macromolécules reste largement hors de portée des outils actuels de modélisation moléculaire. L'objectif de cette thèse est de développer une nouvelle approche basée sur des algorithmes de planification de mouvement issus de la robotique pour mieux traiter la flexibilité moléculaire dans l'étude des interactions protéiques. Nous avons étendu un algorithme récent d'exploration par échantillonnage aléatoire, ML-RRT pour le désassemblage d'objets articulés complexes. Cet algorithme repose sur la décomposition des paramètres de configuration en deux sous-ensembles actifs et passifs, qui sont traités de manière découplée. Les extensions proposées permettent de considérer plusieurs degrés de mobilité pour la partie passive, qui peut être poussée ou attirée par la partie active. Cet outil algorithmique a été appliqué avec succès pour l'étude des changements conformationnels de protéines induits lors de la diffusion d'un ligand. A partir de cette extension, nous avons développé une nouvelle méthode pour la résolution simultanée du séquençage et des mouvements de désassemblage entre plusieurs objets. La méthode, nommée Iterative-ML-RRT, calcule non seulement les trajectoires permettant d'extraire toutes les pièces d'un objet complexe assemblé, mais également l'ordre permettant le désassemblage. L'approche est générale et a été appliquée pour l'étude du processus de dissociation de complexes macromoléculaires en introduisant une fonction d'évaluation basée sur l'énergie d'interaction. Les résultats présentés dans cette thèse montrent non seulement l'efficacité mais aussi la généralité des algorithmes proposés. ABSTRACT : Understanding and predicting structure-function relationships in proteins with fully in silico approaches remain today a great challenge. Despite recent developments of computational methods for studying molecular motions and interactions, dealing with macromolecular flexibility largely remains out of reach of the existing molecular modeling tools. The aim of this thesis is to develop a novel approach based on motion planning algorithms originating from robotics to better deal with macromolecular flexibility in protein interaction studies. We have extended a recent sampling-based algorithm, ML-RRT, for (dis)-assembly path planning of complex articulated objects. This algorithm is based on a partition of the configuration parameters into active and passive subsets, which are then treated in a decoupled manner. The presented extensions permit to consider different levels of mobility for the passive parts that can be pushed or pulled by the motion of active parts. This algorithmic tool is successfully applied to study protein conformational changes induced by the diffusion of a ligand inside it. Building on the extension of ML-RRT, we have developed a novel method for simultaneously (dis)assembly sequencing and path planning. The new method, called Iterative-ML-RRT, computes not only the paths for extracting all the parts from a complex assembled object, but also the preferred order that the disassembly process has to follow. We have applied this general approach for studying disassembly pathways of macromolecular complexes considering a scoring function based on the interaction energy. The results described in this thesis prove not only the efficacy but also the generality of the proposed algorithm
(Dis)assembly path planning for complex objects and applications to structural biology
Understanding and predicting structure-function relationships in proteins with fully in silico approaches remain today a great challenge. Despite recent developments of computational methods for studying molecular motions and interactions, dealing with macromolecular flexibility largely remains out of reach of the existing molecular modeling tools. The aim of this thesis is to develop a novel approach based on motion planning algorithms originating from robotics to better deal with macromolecular flexibility in protein interaction studies. We have extended a recent sampling-based algorithm, ML-RRT, for (dis)-assembly path planning of complex articulated objects. This algorithm is based on a partition of the configuration parameters into active and passive subsets, which are then treated in a decoupled manner. The presented extensions permit to consider different levels of mobility for the passive parts that can be pushed or pulled by the motion of active parts. This algorithmic tool is successfully applied to study protein conformational changes induced by the diffusion of a ligand inside it. Building on the extension of ML-RRT, we have developed a novel method for simultaneously (dis)assembly sequencing and path planning. The new method, called Iterative-ML-RRT, computes not only the paths for extracting all the parts from a complex assembled object, but also the preferred order that the disassembly process has to follow. We have applied this general approach for studying disassembly pathways of macromolecular complexes considering a scoring function based on the interaction energy. The results described in this thesis prove not only the efficacy but also the generality of the proposed algorithm
Incremental Sampling-based Algorithms for Optimal Motion Planning
During the last decade, incremental sampling-based motion planning
algorithms, such as the Rapidly-exploring Random Trees (RRTs) have been shown
to work well in practice and to possess theoretical guarantees such as
probabilistic completeness. However, no theoretical bounds on the quality of
the solution obtained by these algorithms have been established so far. The
first contribution of this paper is a negative result: it is proven that, under
mild technical conditions, the cost of the best path in the RRT converges
almost surely to a non-optimal value. Second, a new algorithm is considered,
called the Rapidly-exploring Random Graph (RRG), and it is shown that the cost
of the best path in the RRG converges to the optimum almost surely. Third, a
tree version of RRG is introduced, called the RRT algorithm, which
preserves the asymptotic optimality of RRG while maintaining a tree structure
like RRT. The analysis of the new algorithms hinges on novel connections
between sampling-based motion planning algorithms and the theory of random
geometric graphs. In terms of computational complexity, it is shown that the
number of simple operations required by both the RRG and RRT algorithms is
asymptotically within a constant factor of that required by RRT.Comment: 20 pages, 10 figures, this manuscript is submitted to the
International Journal of Robotics Research, a short version is to appear at
the 2010 Robotics: Science and Systems Conference
Robotics-Inspired Methods for the Simulation of Conformational Changes in Proteins
Cette thèse présente une approche de modélisation inspirée par la robotique pour l'étude des changements conformationnels des protéines. Cette approche est basée sur une représentation mécanistique des protéines permettant l'application de méthodes efficaces provenant du domaine de la robotique. Elle fournit également une méthode appropriée pour le traitement gros-grains des protéines sans perte de détail au niveau atomique. L'approche présentée dans cette thèse est appliquée à deux types de problèmes de simulation moléculaire. Dans le premier, cette approche est utilisée pour améliorer l'échantillonnage de l'espace conformationnel des protéines. Plus précisément, cette approche de modélisation est utilisée pour implémenter des classes de mouvements pour l'échantillonnage, aussi bien connues que nouvelles, ainsi qu'une stratégie d'échantillonnage mixte, dans le contexte de la méthode de Monte Carlo. Les résultats des simulations effectuées sur des protéines ayant des topologies différentes montrent que cette stratégie améliore l'échantillonnage, sans toutefois nécessiter de ressources de calcul supplémentaires. Dans le deuxième type de problèmes abordés ici, l'approche de modélisation mécanistique est utilisée pour implémenter une méthode inspirée par la robotique et appliquée à la simulation de mouvements de grande amplitude dans les protéines. Cette méthode est basée sur la combinaison de l'algorithme RRT (Rapidly-exploring Random Tree) avec l'analyse en modes normaux, qui permet une exploration efficace des espaces de dimension élevée tels les espaces conformationnels des protéines. Les résultats de simulations effectuées sur un ensemble de protéines montrent l'efficacité de la méthode proposée pour l'étude des transitions conformationnellesProteins are biological macromolecules that play essential roles in living organisms. Un- derstanding the relationship between protein structure, dynamics and function is indis- pensable for advances in fields such as biology, pharmacology and biotechnology. Study- ing this relationship requires a combination of experimental and computational methods, whose development is the object of very active interdisciplinary research. In such a context, this thesis presents a robotics-inspired modeling approach for studying confor- mational changes in proteins. This approach is based on a mechanistic representation of proteins that enables the application of efficient methods originating from the field of robotics. It also provides an accurate method for coarse-grained treatment of proteins without loosing full-atom details.The presented approach is applied in this thesis to two different molecular simulation problems. First, the approach is used to enhance sampling of the conformational space of proteins using the Monte Carlo method. The modeling approach is used to implement new and known Monte Carlo trial move classes as well as a mixed sampling strategy. Results of simulations performed on proteins with different topologies show that this strategy enhances sampling without demanding higher computational resources. In the second problem tackled in this thesis, the mechanistic modeling approach is used to implement a robotics-inspired method for simulating large amplitude motions in proteins. This method is based on the combination of the Rapidly-exploring Random Tree (RRT) algorithm with Normal Mode Analysis (NMA), which allows efficient exploration of the high dimensional conformational spaces of proteins. Results of simulations performed on ten different proteins of different sizes and topologies show the effectiveness of the proposed method for studying conformational transitionsTOULOUSE-INSA-Bib. electronique (315559905) / SudocSudocFranceF
Motion planning for geometric models in data visualization
Interaktivní geometrické modely pro simulaci přírodních jevů (LH11006)Pokročilé grafické a počítačové systémy (SGS-2016-013)A finding of path is an important task in many research areas and it is
a common problem solved in a wide range of applications. New problems of
finding path appear and complex problems persist, such as a real-time plan-
ning of paths for huge crowds in dynamic environments, where the properties
according to which the cost of a path is evaluated as well as the topology
of paths may change. The task of finding a path can be divided into path
planning and motion planning, which implicitly respects the collision with
surroundings in the environment.
Within the first group this thesis focuses on path planning on graphs for
crowds. The main idea is to group members of the crowd by their common
initial and target positions and then plan the path for one representative
member of each group. These representative members can be navigated by
classic approaches and the rest of the group will follow them. If the crowd can
be divided into a few groups this way, the proposed approach will save a huge
amount of computational and memory demands in dynamic environments.
In the second area, motion planning, we are dealing with another problem.
The task is to navigate the ligand through the protein or into the protein,
which turns out to be a challenging problem because it needs to be solved in
3D with the collision detection
Sampling-Based Motion Planning: A Comparative Review
Sampling-based motion planning is one of the fundamental paradigms to
generate robot motions, and a cornerstone of robotics research. This
comparative review provides an up-to-date guideline and reference manual for
the use of sampling-based motion planning algorithms. This includes a history
of motion planning, an overview about the most successful planners, and a
discussion on their properties. It is also shown how planners can handle
special cases and how extensions of motion planning can be accommodated. To put
sampling-based motion planning into a larger context, a discussion of
alternative motion generation frameworks is presented which highlights their
respective differences to sampling-based motion planning. Finally, a set of
sampling-based motion planners are compared on 24 challenging planning
problems. This evaluation gives insights into which planners perform well in
which situations and where future research would be required. This comparative
review thereby provides not only a useful reference manual for researchers in
the field, but also a guideline for practitioners to make informed algorithmic
decisions.Comment: 25 pages, 7 figures, Accepted for Volume 7 (2024) of the Annual
Review of Control, Robotics, and Autonomous System
Rapid Sampling of Molecular Motions with Prior Information Constraints
Proteins are active, flexible machines that perform a range of different
functions. Innovative experimental approaches may now provide limited partial
information about conformational changes along motion pathways of proteins.
There is therefore a need for computational approaches that can efficiently
incorporate prior information into motion prediction schemes. In this paper, we
present PathRover, a general setup designed for the integration
of prior information into the motion planning algorithm of rapidly exploring
random trees (RRT). Each suggested motion pathway comprises a sequence of
low-energy clash-free conformations that satisfy an arbitrary number of prior
information constraints. These constraints can be derived from experimental data
or from expert intuition about the motion. The incorporation of prior
information is very straightforward and significantly narrows down the vast
search in the typically high-dimensional conformational space, leading to
dramatic reduction in running time. To allow the use of state-of-the-art energy
functions and conformational sampling, we have integrated this framework into
Rosetta, an accurate protocol for diverse types of structural modeling. The
suggested framework can serve as an effective complementary tool for molecular
dynamics, Normal Mode Analysis, and other prevalent techniques for predicting
motion in proteins. We applied our framework to three different model systems.
We show that a limited set of experimentally motivated constraints may
effectively bias the simulations toward diverse predicates in an outright
fashion, from distance constraints to enforcement of loop closure. In
particular, our analysis sheds light on mechanisms of protein domain swapping
and on the role of different residues in the motion
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