Lydia Tapia

Simulating protein motions with rigidity analysis

Protein motions, ranging from molecular flexibility to large-scale conformational change, play an essential role in many biochemical processes. Despite the explosion in our knowledge of structural and functional data, our understanding of protein movement is still very limited. In previous work, we developed and validated a motion planning based method for mapping protein folding pathways from unstructured conformations to the native state. In this paper, we propose a novel method based on rigidity theory to sample conformation space more effectively, and we describe extensions of our framework to automate the process and to map transitions between specified conformations. Our results show that these additions both improve the accuracy of our maps and enable us to study a broader range of motions for larger proteins. For example, we show that rigidity-based sampling results in maps that capture subtle folding differences between protein G and its mutants, NuG1 and NuG2, and we illustrate how our technique can be used to study large-scale conformational changes in calmodulin, a 148 residue signaling protein known to undergo conformational changes when binding to Ca(2+). Finally, we announce our web-based protein folding server which includes a publicly available archive of protein motions: (http://parasol.tamu.edu/foldingserver/).

Design and Implementation of a Virtual Reality System and Its Application to Training Medical First Responders

This paper presents the design and implementation of a distributed virtual reality (VR) platform that was developed to support the training of multiple users who must perform complex tasks in which situation assessment and critical thinking are the primary components of success. The system is fully immersive and multimodal, and users are represented as tracked, full-body figures. The system supports the manipulation of virtual objects, allowing users to act upon the environment in a natural manner. The underlying intelligent simulation component creates an interactive, responsive world in which the consequences of such actions are presented within a realistic, time-critical scenario. The focus of this work has been on the training of medical emergency-response personnel. BioSimMER, an application of the system to training first responders to an act of bio-terrorism, has been implemented and is presented throughout the paper as a concrete example of how the underlying platform architecture supports complex training tasks. Finally, a preliminary field study was performed at the Texas Engineering Extension Service Fire Protection Training Division. The study focused on individual, rather than team, interaction with the system and was designed to gauge user acceptance of VR as a training tool. The results of this study are presented.

Simulating RNA folding kinetics on approximated energy landscapes.

We present a general computational approach to simulate RNA folding kinetics that can be used to extract population kinetics, folding rates and the formation of particular substructures that might be intermediates in the folding process. Simulating RNA folding kinetics can provide unique insight into RNA whose functions are dictated by folding kinetics and not always by nucleotide sequence or the structure of the lowest free-energy state. The method first builds an approximate map (or model) of the folding energy landscape from which the population kinetics are analyzed by solving the master equation on the map. We present results obtained using an analysis technique, map-based Monte Carlo simulation, which stochastically extracts folding pathways from the map. Our method compares favorably with other computational methods that begin with a comprehensive free-energy landscape, illustrating that the smaller, approximate map captures the major features of the complete energy landscape. As a result, our method scales to larger RNAs. For example, here we validate kinetics of RNA of more than 200 nucleotides. Our method accurately computes the kinetics-based functional rates of wild-type and mutant ColE1 RNAII and MS2 phage RNAs showing excellent agreement with experiment.

Simulating protein motions with rigidity analysis.

Protein motions, ranging from molecular flexibility to large-scale conformational change, play an essential role in many biochemical processes. Despite the explosion in our knowledge of structural and functional data, our understanding of protein movement is still very limited. In previous work, we developed and validated a motion planning based method for mapping protein folding pathways from unstructured conformations to the native state. In this paper, we propose a novel method based on rigidity theory to sample conformation space more effectively, and we describe extensions of our framework to automate the process and to map transitions between specified conformations. Our results show that these additions both improve the accuracy of our maps and enable us to study a broader range of motions for larger proteins. For example, we show that rigidity-based sampling results in maps that capture subtle folding differences between protein G and its mutants, NuG1 and NuG2, and we illustrate how our technique can be used to study large-scale conformational changes in calmodulin, a 148 residue signaling protein known to undergo conformational changes when binding to Ca(2+). Finally, we announce our web-based protein folding server which includes a publicly available archive of protein motions: (http://parasol.tamu.edu/foldingserver/).

Learning swing-free trajectories for UAVs with a suspended load

Attaining autonomous flight is an important task in aerial robotics. Often flight trajectories are not only subject to unknown system dynamics, but also to specific task constraints. This paper presents a motion planning method for generating trajectories with minimal residual oscillations (swing-free) for rotorcraft carrying a suspended loads. We rely on a finite-sampling, batch reinforcement learning algorithm to train the system for a particular load. We find criteria that allow the trained agent to be transferred to a variety of models, state and action spaces and produce a number of different trajectories. Through a combination of simulations and experiments, we demonstrate that the inferred policy is robust to noise and the unmodeled dynamics of the system. The contributions of this work are 1) applying reinforcement learning to solve the problem of finding swing-free trajectories for rotorcraft, 2) designing a problem-specific feature vector for value function approximation, 3) giving sufficient conditions for successful learning transfer to different models, state and action spaces, and 4) verification of the resulting trajectories in both simulation and autonomous control of quadrotors with suspended loads.

A reinforcement learning approach towards autonomous suspended load manipulation using aerial robots

In this paper, we present a problem where a suspended load, carried by a rotorcraft aerial robot, performs trajectory tracking. We want to accomplish this by specifying the reference trajectory for the suspended load only. The aerial robot needs to discover/learn its own trajectory which ensures that the suspended load tracks the reference trajectory. As a solution, we propose a method based on least-square policy iteration (LSPI) which is a type of reinforcement learning algorithm. The proposed method is verified through simulation and experiments.

Path-guided artificial potential fields with stochastic reachable sets for motion planning in highly dynamic environments

Highly dynamic environments pose a particular challenge for motion planning due to the need for constant evaluation or validation of plans. However, due to the wide range of applications, an algorithm to safely plan in the presence of moving obstacles is required. In this paper, we propose a novel technique that provides computationally efficient planning solutions in environments with static obstacles and several dynamic obstacles with stochastic motions. Path-Guided APF-SR works by first applying a sampling-based technique to identify a valid, collision-free path in the presence of static obstacles. Then, an artificial potential field planning method is used to safely navigate through the moving obstacles using the path as an attractive intermediate goal bias. In order to improve the safety of the artificial potential field, repulsive potential fields around moving obstacles are calculated with stochastic reachable sets, a method previously shown to significantly improve planning success in highly dynamic environments. We show that Path-Guided APF-SR outperforms other methods that have high planning success in environments with 300 stochastically moving obstacles. Furthermore, planning is achievable in environments in which previously developed methods have failed.

Kinetics analysis methods for approximate folding landscapes

MOTIVATION Protein motions play an essential role in many biochemical processes. Lab studies often quantify these motions in terms of their kinetics such as the speed at which a protein folds or the population of certain interesting states like the native state. Kinetic metrics give quantifiable measurements of the folding process that can be compared across a group of proteins such as a wild-type protein and its mutants. RESULTS We present two new techniques, map-based master equation solution and map-based Monte Carlo simulation, to study protein kinetics through folding rates and population kinetics from approximate folding landscapes, models called maps. From these two new techniques, interesting metrics that describe the folding process, such as reaction coordinates, can also be studied. In this article we focus on two metrics, formation of helices and structure formation around tryptophan residues. These two metrics are often studied in the lab through circular dichroism (CD) spectra analysis and tryptophan fluorescence experiments, respectively. The approximated landscape models we use here are the maps of protein conformations and their associated transitions that we have presented and validated previously. In contrast to other methods such as the traditional master equation and Monte Carlo simulation, our techniques are both fast and can easily be computed for full-length detailed protein models. We validate our map-based kinetics techniques by comparing folding rates to known experimental results. We also look in depth at the population kinetics, helix formation and structure near tryptophan residues for a variety of proteins. AVAILABILITY We invite the community to help us enrich our publicly available database of motions and kinetics analysis by submitting to our server: http://parasol.tamu.edu/foldingserver/.

C-space Subdivision and Integration in Feature-Sensitive Motion Planning

There are many randomized motion planning techniques, but it is often difficult to determine what planning method to apply to best solve a problem. Planners have their own strengths and weaknesses, and each one is best suited to a specific type of problem. In previous work, we proposed a meta-planner that, through analysis of the problem features, subdivides the instance into regions and determines which planner to apply in each region. The results obtained with our prototype system were very promising even though it utilized simplistic strategies for all components. Even so, we did determine that strategies for problem subdivision and for combination of partial regional solutions have a crucial impact on performance. In this paper, we propose new methods for these steps to improve the performance of the meta-planner. For problem subdivision, we propose two new methods: a method based on ‘ gaps’ and a method based on information theory. For combining partial solutions, we propose two new methods that concentrate on neighboring areas of the regional solutions. We present results that show the performance gain achieved by utilizing these new strategies.

Automated Aerial Suspended Cargo Delivery through Reinforcement Learning

Abstract Cargo-bearing unmanned aerial vehicles (UAVs) have tremendous potential to assist humans by delivering food, medicine, and other supplies. For time-critical cargo delivery tasks, UAVs need to be able to quickly navigate their environments and deliver suspended payloads with bounded load displacement. As a constraint balancing task for joint UAV-suspended load system dynamics, this task poses a challenge. This article presents a reinforcement learning approach for aerial cargo delivery tasks in environments with static obstacles. We first learn a minimal residual oscillations task policy in obstacle-free environments using a specifically designed feature vector for value function approximation that allows generalization beyond the training domain. The method works in continuous state and discrete action spaces. Since planning for aerial cargo requires very large action space (over 106 actions) that is impractical for learning, we define formal conditions for a class of robotics problems where learning can occur in a simplified problem space and successfully transfer to a broader problem space. Exploiting these guarantees and relying on the discrete action space, we learn the swing-free policy in a subspace several orders of magnitude smaller, and later develop a method for swing-free trajectory planning along a path. As an extension to tasks in environments with static obstacles where the load displacement needs to be bounded throughout the trajectory, sampling-based motion planning generates collision-free paths. Next, a reinforcement learning agent transforms these paths into trajectories that maintain the bound on the load displacement while following the collision-free path in a timely manner. We verify the approach both in simulation and in experiments on a quadrotor with suspended load and verify the methods safety and feasibility through a demonstration where a quadrotor delivers an open container of liquid to a human subject. The contributions of this work are two-fold. First, this article presents a solution to a challenging, and vital problem of planning a constraint-balancing task for an inherently unstable non-linear system in the presence of obstacles. Second, AI and robotics researchers can both benefit from the provided theoretical guarantees of system stability on a class of constraint-balancing tasks that occur in very large action spaces.