Docking and small angle X-ray scattering studies of purine nucleoside phosphorylase

Docking simulations have been used to assess protein complexes with some success. Small angle X-ray scattering (SAXS) is a well-established technique to investigate protein spatial configuration. This work describes the integration of geometric docking with SAXS to investigate the quaternary structure of recombinant human purine nucleoside phosphorylase (PNP). This enzyme catalyzes the reversible phosphorolysis of N-ribosidic bonds of purine nucleosides and deoxynucleosides. A genetic deficiency due to mutations in the gene encoding for PNP causes gradual decrease in T-cell immunity. Inappropriate activation of T-cells has been implicated in several clinically relevant human conditions such as transplant rejection, rheumatoid arthritis, lupus, and T-cell lymphomas. PNP is therefore a target for inhibitor development aiming at T-cell immune response modulation and has been submitted to extensive structure-based drug design. The present analysis confirms the trimeric structure observed in the crystal. The potential application of the present procedure to other systems is discussed. (C) 2003 Elsevier B.V. All rights reserved.

Molecular modeling databases: A new way in the search of protein targets for drug development

DBMODELING is a relational database of annotated comparative protein structure models and their metabolic, pathway characterization. It is focused on enzymes identified in the genomes of Mycobacterium tuberculosis and Xylella fastidiosa. The main goal of the present database is to provide structural models to be used in docking simulations and drug design. However, since the accuracy of structural models is highly dependent on sequence identity between template and target, it is necessary to make clear to the user that only models which show high structural quality should be used in such efforts. Molecular modeling of these genomes generated a database, in which all structural models were built using alignments presenting more than 30% of sequence identity, generating models with medium and high accuracy. All models in the database are publicly accessible at http://www.biocristalografia.df.ibilce.unesp.br/tools. DBMODELING user interface provides users friendly menus, so that all information can be printed in one stop from any web browser. Furthermore, DBMODELING also provides a docking interface, which allows the user to carry out geometric docking simulation, against the molecular models available in the database. There are three other important homology model databases: MODBASE, SWISSMODEL, and GTOP. The main applications of these databases are described in the present article. © 2007 Bentham Science Publishers Ltd.

Using Correlated Parameters for Improved Ranking of Protein-Protein Docking Decoys

A successful protein-protein docking study culminates in identification of decoys at top ranks with near-native quaternary structures. However, this task remains enigmatic because no generalized scoring functions exist that effectively infer decoys according to the similarity to near-native quaternary structures. Difficulties arise because of the highly irregular nature of the protein surface and the significant variation of the nonbonding and solvation energies based on the chemical composition of the protein-protein interface. In this work, we describe a novel method combining an interface-size filter, a regression model for geometric compatibility (based on two correlated surface and packing parameters), and normalized interaction energy (calculated from correlated nonbonded and solvation energies), to effectively rank decoys from a set of 10,000 decoys. Tests on 30 unbound binary protein-protein complexes show that in 16 cases we can identify at least one decoy in top three ranks having <= 10 angstrom backbone root mean square deviation from true binding geometry. Comparisons with other state-of-art methods confirm the improved ranking power of our method without the use of any experiment-guided restraints, evolutionary information, statistical propensities, or modified interaction energy equations. Tests on 118 less-difficult bound binary protein-protein complexes with <= 35% sequence redundancy at the interface showed that in 77% cases, at least 1 in 10,000 decoys were identified with <= 5 angstrom backbone root mean square deviation from true geometry at first rank. The work will promote the use of new concepts where correlations among parameters provide more robust scoring models. It will facilitate studies involving molecular interactions, including modeling of large macromolecular assemblies and protein structure prediction. (C) 2010 Wiley Periodicals, Inc. J Comput Chem 32: 787-796, 2011.

PRUNE and PROBE-two modular web services for protein-protein docking

The protein-protein docking programs typically perform four major tasks: (i) generation of docking poses, (ii) selecting a subset of poses, (iii) their structural refinement and (iv) scoring, ranking for the final assessment of the true quaternary structure. Although the tasks can be integrated or performed in a serial order, they are by nature modular, allowing an opportunity to substitute one algorithm with another. We have implemented two modular web services, (i) PRUNE: to select a subset of docking poses generated during sampling search (http://pallab.serc.iisc.ernet.in/prune) and (ii) PROBE: to refine, score and rank them (http://pallab.serc.iisc.ernet.in/probe). The former uses a new interface area based edge-scoring function to eliminate > 95% of the poses generated during docking search. In contrast to other multi-parameter-based screening functions, this single parameter based elimination reduces the computational time significantly, in addition to increasing the chances of selecting native-like models in the top rank list. The PROBE server performs ranking of pruned poses, after structure refinement and scoring using a regression model for geometric compatibility, and normalized interaction energy. While web-service similar to PROBE is infrequent, no web-service akin to PRUNE has been described before. Both the servers are publicly accessible and free for use.

A Vision Based Target Detection System for Docking of an Autonomous Underwater Vehicle

This paper describes the development and preliminary experimental evaluation of a visionbased docking system to allow an Autonomous Underwater Vehicle (AUV) to identify and attach itself to a set of uniquely identifiable targets. These targets, docking poles, are detected using Haar rectangular features and rotation of integral images. A non-holonomic controller allows the Starbug AUV to orient itself with respect to the target whilst maintaining visual contact during the manoeuvre. Experimental results show the proposed vision system is capable of robustly identifying a pair of docking poles simultaneously in a variety of orientations and lighting conditions. Experiments in an outdoor pool show that this vision system enables the AUV to dock autonomously from a distance of up to 4m with relatively low visibility.

A geometric approach to trajectory design for an autonomous underwater vehicle : surveying the bulbous bow of a ship

In this paper, we present a control strategy design technique for an autonomous underwater vehicle based on solutions to the motion planning problem derived from differential geometric methods. The motion planning problem is motivated by the practical application of surveying the hull of a ship for implications of harbor and port security. In recent years, engineers and researchers have been collaborating on automating ship hull inspections by employing autonomous vehicles. Despite the progresses made, human intervention is still necessary at this stage. To increase the functionality of these autonomous systems, we focus on developing model-based control strategies for the survey missions around challenging regions, such as the bulbous bow region of a ship. Recent advances in differential geometry have given rise to the field of geometric control theory. This has proven to be an effective framework for control strategy design for mechanical systems, and has recently been extended to applications for underwater vehicles. Advantages of geometric control theory include the exploitation of symmetries and nonlinearities inherent to the system. Here, we examine the posed inspection problem from a path planning viewpoint, applying recently developed techniques from the field of differential geometric control theory to design the control strategies that steer the vehicle along the prescribed path. Three potential scenarios for surveying a ship?s bulbous bow region are motivated for path planning applications. For each scenario, we compute the control strategy and implement it onto a test-bed vehicle. Experimental results are analyzed and compared with theoretical predictions.

A first extension of geometric control theory to underwater vehicles

This paper serves as a first study on the implementation of control strategies developed using a kinematic reduction onto test bed autonomous underwater vehicles (AUVs). The equations of motion are presented in the framework of differential geometry, including external dissipative forces, as a forced affine connection control system. We show that the hydrodynamic drag forces can be included in the affine connection, resulting in an affine connection control system. The definitions of kinematic reduction and decoupling vector field are thus extended from the ideal fluid scenario. Control strategies are computed using this new extension and are reformulated for implementation onto a test-bed AUV. We compare these geometrically computed controls to time and energy optimal controls for the same trajectory which are computed using a previously developed algorithm. Through this comparison we are able to validate our theoretical results based on the experiments conducted using the time and energy efficient strategies.

Geometric Control Theory and its Application to Underwater Vehicles

This dissertation is based on theoretical study and experiments which extend geometric control theory to practical applications within the field of ocean engineering. We present a method for path planning and control design for underwater vehicles by use of the architecture of differential geometry. In addition to the theoretical design of the trajectory and control strategy, we demonstrate the effectiveness of the method via the implementation onto a test-bed autonomous underwater vehicle. Bridging the gap between theory and application is the ultimate goal of control theory. Major developments have occurred recently in the field of geometric control which narrow this gap and which promote research linking theory and application. In particular, Riemannian and affine differential geometry have proven to be a very effective approach to the modeling of mechanical systems such as underwater vehicles. In this framework, the application of a kinematic reduction allows us to calculate control strategies for fully and under-actuated vehicles via kinematic decoupled motion planning. However, this method has not yet been extended to account for external forces such as dissipative viscous drag and buoyancy induced potentials acting on a submerged vehicle. To fully bridge the gap between theory and application, this dissertation addresses the extension of this geometric control design method to include such forces. We incorporate the hydrodynamic drag experienced by the vehicle by modifying the Levi-Civita affine connection and demonstrate a method for the compensation of potential forces experienced during a prescribed motion. We present the design method for multiple different missions and include experimental results which validate both the extension of the theory and the ability to implement control strategies designed through the use of geometric techniques. By use of the extension presented in this dissertation, the underwater vehicle application successfully demonstrates the applicability of geometric methods to design implementable motion planning solutions for complex mechanical systems having equal or fewer input forces than available degrees of freedom. Thus, we provide another tool with which to further increase the autonomy of underwater vehicles.

Controlling a submerged rigid body : a geometric analysis

In this paper we analyze the equations of motion of a submerged rigid body. Our motivation is based on recent developments done in trajectory design for this problem. Our goal is to relate some properties of singular extremals to the existence of decoupling vector fields. The ideas displayed in this paper can be viewed as a starting point to a geometric formulation of the trajectory design problem for mechanical systems with potential and external forces.

Geometric and force relationships for the development of a scaled model hydraulic excavator

Hydraulic excavators in the mining industry are widely used owing to the large payload capabilities these machines can achieve. However, there are very few optimisation studies for producing efficient hydraulic excavator backets. An efficient bucket can avoid unnecessary weight; greatly influence the payload and optimise the efficiency of hydraulic mining excavators. This paper presents a framework for the development of a scaled hydraulic excavator by examining the geometry and force relationships. A small hydraulic excavator was purchased and fitted with a broom scaled to a factor. Geometric and force relationships of the model were derived to assist computer instrumentation to retrieve necessary variable input for bucket design.

The geometric modelling of social frames and contexts

How do humans respond to their social context? This question is becoming increasingly urgent in a society where democracy requires that the citizens of a country help to decide upon its policy directions, and yet those citizens frequently have very little knowledge of the complex issues that these policies seek to address. Frequently, we find that humans make their decisions more with reference to their social setting, than to the arguments of scientists, academics, and policy makers. It is broadly anticipated that the agent based modelling (ABM) of human behaviour will make it possible to treat such social effects, but we take the position here that a more sophisticated treatment of context will be required in many such models. While notions such as historical context (where the past history of an agent might affect its later actions) and situational context (where the agent will choose a different action in a different situation) abound in ABM scenarios, we will discuss a case of a potentially changing context, where social effects can have a strong influence upon the perceptions of a group of subjects. In particular, we shall discuss a recently reported case where a biased worm in an election debate led to significant distortions in the reports given by participants as to who won the debate (Davis et al 2011). Thus, participants in a different social context drew different conclusions about the perceived winner of the same debate, with associated significant differences among the two groups as to who they would vote for in the coming election. We extend this example to the problem of modelling the likely electoral responses of agents in the context of the climate change debate, and discuss the notion of interference between related questions that might be asked of an agent in a social simulation that was intended to simulate their likely responses. A modelling technology which could account for such strong social contextual effects would benefit regulatory bodies which need to navigate between multiple interests and concerns, and we shall present one viable avenue for constructing such a technology. A geometric approach will be presented, where the internal state of an agent is represented in a vector space, and their social context is naturally modelled as a set of basis states that are chosen with reference to the problem space.

A mask-based approach for the geometric calibration of thermal-infrared cameras

Accurate and efficient thermal-infrared (IR) camera calibration is important for advancing computer vision research within the thermal modality. This paper presents an approach for geometrically calibrating individual and multiple cameras in both the thermal and visible modalities. The proposed technique can be used to correct for lens distortion and to simultaneously reference both visible and thermal-IR cameras to a single coordinate frame. The most popular existing approach for the geometric calibration of thermal cameras uses a printed chessboard heated by a flood lamp and is comparatively inaccurate and difficult to execute. Additionally, software toolkits provided for calibration either are unsuitable for this task or require substantial manual intervention. A new geometric mask with high thermal contrast and not requiring a flood lamp is presented as an alternative calibration pattern. Calibration points on the pattern are then accurately located using a clustering-based algorithm which utilizes the maximally stable extremal region detector. This algorithm is integrated into an automatic end-to-end system for calibrating single or multiple cameras. The evaluation shows that using the proposed mask achieves a mean reprojection error up to 78% lower than that using a heated chessboard. The effectiveness of the approach is further demonstrated by using it to calibrate two multiple-camera multiple-modality setups. Source code and binaries for the developed software are provided on the project Web site.

A geometric construction of travelling wave solutions to the Keller–Segel model

We study a version of the Keller–Segel model for bacterial chemotaxis, for which exact travelling wave solutions are explicitly known in the zero attractant diffusion limit. Using geometric singular perturbation theory, we construct travelling wave solutions in the small diffusion case that converge to these exact solutions in the singular limit.