Precision Docking Research Articles

An Automated Transport Management System

Transport demand in most Indian cities has increased significantly due to increase in population as a result of both natural increase and migration from rural areas and smaller towns fast growth of India's population like other developing countries has trigger a greater need for used organized public transport system. Automation of bus transport has been gaining more importance because they provide accurate information of buses like reservation, air charges, route information, bus information etc anywhere and anytime. The dissertation has been divided into six modules based on the functionalities of the system namely, information system module, reservation system module. Administartive management system module, fleet management system module, and warehouse module and financial module. These modules have been designed to build up an integrated system to cover various aspects of automated bus transport management system. They provide full information about the bus enquiry, buses schedules, buses fairs, buses ticket reservation, buses time table enquiry. Objectives of the Proposed Research Work: The main objective behind developing this software is to ease managed bus transportation system. Various modules are used in this dissertation. All function of modules can be developed in this program that is ease to passenger work. Software for managing transportation operations of all types: shippers, airlines, bus, train, taxi, moving companies, transportation rental agencies, etc. These programs feature modules for tracking and managing every aspect of vehicle maintenance, fuel costing, routing and mapping, warehousing, communications, EDI implementations, traveler and cargo handling, carrier selection and management, accounting, etc. The benefits that automation technology can provide, beyond those achievable with conventional, non- automated bus operations, include: Permitting precision docking at bus stops, so that physically impaired passengers can more easily gain access to and from the buses and speeding up the loading and unloading processes for all passengers:  Facilitating maintenance operations and saving labor? ordinarily used to move buses through routine overnight maintenance and cleaning processes;  Smoother and safer travel for passengers, increasing passenger riding comfort and reducing crash costs for operators; significantly higher vehicle and passenger capacity per lane, by enabling buses to operate at shorter headway than under manual driver control;  Reduced fuel consumption and emissions for buses that can operate in automated platoons with small enough separations (half vehicle length or less) that aerodynamic drag can be reduced significantly;  Potentially reduced driver labor costs for the portion of the bus trip that operates on the automated lane. These six modules have different work in this dissertation:- Information Management System:

In-silico identification of potential antagonists for human Casein kinase II subunit alpha' (CK2α2)

AbstractHuman CK2α2 is an enzyme that belongs to the Serine/Threonine protein kinase family which is involved in signal transduction. Over expression of CK2α2 causes kidney cancer therefore, human CK2α2 has been identified as a drug target for the development of potential antagonists against cancer therapy. The existing human CK2α2 inhibitors in clinical practice are having side effects like fatigue, diarrhea, nausea, anorexia and vomiting. High-throughput virtual screening is one of the most common method used to identify lead compounds was implemented in the present study to identify potential inhibitors of human CK2α2. The co-crystal structure of human CK2α2 was retrieved from the protein data bank. A 2D similarity search was performed for available five human CK2α2 inhibitors (Apigenin, VX680, Sunitinib, SUI4813 and CCK) taken from PDB and PubMed to acquire 1942 structural analogs. The 3D structural conversion and multiple confirmations for 1942 compounds were generated using LigPrep. The docking and scoring calculations were performed using Glide v5.7 which includes high throughput virtual screening (HTVS), Standard precision (SP) docking and extra precision (XP) docking. Obtained 39 leads were compared with docking scores of the existing inhibitors and proposed six leads having good binding affinity. The binding orientation of CK2α2-lead 1complex was correlating with native co-crystal structure. Hence, lead ‘1’ can be suggested as potent inhibitor against human CK2α2 involved in kidney cancer.

Identification of new leads for human IGFBP-2: a therapeutic target for cardiovascular diseases

AbstractIGFBP-2, the largest member of insulin-like growth factor binding proteins family, is under-expressed in hazardous cardiovascular diseases like obesity and type II diabetes mellitus, which upon aging leads to heart stroke. Therefore, IGFBP-2 has been proposed as a possible target for the development of novel leads for cardiovascular disease therapy. High-throughput virtual screening, one of the most common methods used to identify lead compounds was implemented here to identify potential IGFBP-2 activators. The NMR (nuclear magnetic resonance) structure of human IGFBP-2 was retrieved from the protein data bank. A 2D similarity search was performed for known IGFBP-2 activator TPA to acquire 383 structural analogs. The 3D structural conversion and multiple confirmations for 383 compounds were generated using LigPrep with ADME constraints. The docking and scoring calculations were performed using Glide v5.7. The extra precision (XP) docking reported 35 leads and ranked based on XP Gscore. Eleven leads having better XP Gscore compared to TPA were proposed as potential IGFBP-2 activators. Lead ’1’ (3,11-dihydroxyl-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopenta [a] phenon) showed highest XP Gscore of -7.239 kcal/mol, good pharmacological properties and similar molecular interaction as TPA with IGFBP-2. Therefore, lead 1 was proposed as a promising lead of IGFBP-2 for the development of cardiovascular disease therapeutics.

Docking-based virtual screening for the exploration of potential antagonists for human IGFBP6

AbstractDesign of potential drug-like candidates for cardiovascular therapy is of interest in recent years. Elevated level of IGFBP-6 leads to perilous diseases like atherosclerosis, high output cardiac failure and myocardial infarction. The current IGFBP-6 inhibitors available in clinical practice are not having satisfactory anti-cardiovascular effects, leaving room for further improvement. Therefore, with an aim to propose a potent inhibitor to arrest the cardiovascular disease caused by IGFBP-6, tools of computer-aided drug designing were used for virtual screening from small molecule databases. Accordingly, IGFBP-6 tertiary structure was solved through nuclear magnetic resonance techniques retrieved from the protein data bank. Fifteen IGFBP-6 inhibitors were acquired from literature databases and subsequent 2D searching protocol of Ligand.Info yielded 5759 structural analogs. The 3D structural conversion and multiple conformations for each compound were generated using LigPrep with constraints of ADME evaluation and toxicity assessments. The docking and scoring calculations were performed using Glide v5.7. The Glide extra precision (XP) docking had reported 138 leads and ranked based on XP Gscore. Six leads having better XP Gscore compared to current IGFBP-6 inhibitors were proposed as potential inhibitors. Chelidamic acid showed the highest XP Gscore (-7.094 Kcal/mol) with good pharmacological properties and molecular interaction with IGFBP-6. Therefore, chelidamic acid is proposed for rational drug design towards cardiovascular therapy.

Prediction of novel inhibitors for human RNase1 involved in cardiovascular disease through in silico screening

AbstractHuman pancreatic ribonuclease (RNase1) is a small digestive and pyramidine specific enzyme secreted by the pancreas. RNase1 contributes in the regulation of extracellular RNA by hydrolyzing RNA phosphodiester bonds. High levels of RNase1 in cardiovascular disease patients project the enzyme as an attractive drug target. The known RNase1 inhibitors, citric acid and U1S were searched for structural analogs from Ligand.info database to compile 783 ligands. The ligands' 3D structures and their tautomeric states were generated using LigPrep. The 3424 prepared conformations were subjected to QikProp analysis and filtered based on Lipinski rule of five and zero reactive functional group. The 3376 conformations with good ADME (absorption, desorption, metabolism, excretion) profile were passed through multistage docking in virtual screening workflow of Schrodinger software 2011. Seventy five ligands with good binding affinity towards RNase1 were ranked based on XPGscore, through Glide extra precision (XP) docking. Twenty three ligands with better XPGscore compared to published inhibitors (citric acid and U1S) were proposed as potential RNase1 inhibitors. Analysis of docking complexes, their binding orientations, XPGscores and through stringent correlation with published data lead ‘1’ that showed least XPGscore (-12.284 Kcal/mol) was proposed as the best molecule to consider for rational drug designing for treatment of cardiovascular disease.

AUTOMATED DRIVING SYSTEMS: COMMON GROUND OF AUTOMOBILES AND ROBOTS

This article reviews R&D activities on automated highway systems (AHSs) since 1950s with emphasis on recent ones. AHSs in the 1950s and 1960s were featured by a cooperative system between roads and vehicles; those in the 1970s and 1980s were by autonomous systems. Intelligent transport system (ITS) projects since 1980s regarded AHS as an important system, not only a single automated vehicle but also an automated platoon were developed. In recent years, the R&D focuses on automated transit buses aiming at precision docking and driving along a narrow lane and automated truck platoons aiming at energy saving. The automated driving can be common ground of automobiles and robots.

Virtual Fragment Docking by Glide: a Validation Study on 190 Protein−Fragment Complexes

The docking accuracy of Glide was evaluated using 16 different docking protocols on 190 protein-fragment complexes representing 78 targets. Standard precision docking (Glide SP) based protocols showed the best performance. The average root-mean-square deviation (rmsd) between the docked and cocrystallized poses achieved by Glide SP with pre- and postprocessing was 1.17 A, and an acceptable binding mode with rmsd < 2 A could be found in 80% of the cases. Comparison of the docking results produced by different protocols suggests that the sampling efficacy of Glide is adequate for fragment docking. The docking accuracy seems to be limited by the performance of scoring schemes, which is supported by the weak correlation between experimental binding affinities and GlideScores. Cross-docking experiments performed on 8 targets represented by 63 complexes revealed that Glide SP gave similar results to that of the computationally more intensive Glide XP. The average rmsd achieved by Glide SP with pre- and postprocessing was 2.06 A, and an acceptable binding mode with rmsd < 2 A could be found in 63% of the cases. These cross-docking results were improved significantly selecting the optimal X-ray structure for each target (average rmsd = 1.3 A, success rate = 77%), indicating the importance of enrichment studies and the use of multiple X-ray structures in virtual fragment screening.

Pneumatic Brake Control for Precision Stopping of Heavy-Duty Vehicles

Precision stopping is an important automated vehicle control function that is critical in applications such as precision bus docking, automated truck or bus fueling, as well as automatic intersection, or toll booth stopping. The initial applications of this technology are most likely to be applied to heavy-duty vehicles such as buses or trucks. Such applications require specific attention to brake control since the characteristics of a typical pneumatic brake system of a heavy vehicle is inherently nonlinear with large uncertainties. The feasibility of providing a smooth precision stopping brake control based on a conventional pneumatic brake system has not yet been demonstrated. This paper describes the precision stopping problem, verifies the pneumatic brake model, details the indirect adaptive robust control (IARC) design for a pneumatic brake system, and reports the successful implementation of a bus precision docking demonstration

A high precision ultrasonic docking system used for automatic guided vehicle

With the more and more wide applications of automatic guided vehicle (AGV) in the material handling of modern manufactory system, its docking techniques have drawn extensive attention. The objective of this paper is to investigate the ultrasonic sensor based AGV 2D docking. As an established and cost-effective method, the application of classic ultrasonic sensor still faces certain drawbacks, e.g., low accuracy. In the present work, a novel high-precision, low-cost ultrasonic docking system is developed to locate the AGV relative to the docking workstation. In the proposed scheme, with electromagnetic wave used as system synchronization to trigger the time of flight (TOF) counter, the docking system consists of the ultrasound reception and emission beacons positioned at the same height of docking workstation and AGV, respectively. The 2D position of AGV is obtained from the TOF of ultrasonic signal from the emitter to two receivers. To ensure docking accuracy on low-cost narrow bandwidth ultrasonic transducer, a transducer equalizer based on the adaptive training algorithm is employed to realize high ranging precision (1 mm). Experimental results obtained on a demo AGV are presented and discussed, confirming the validity of the proposed solution, with an AGV docking precision of around ±3 mm in x and y, ±1° in bearing.

Driving Assistance during Bus Docking and Mental Load

The aim of the experiment was to test the effect of an automated system of bus docking on drivers' mental workload, to guarantee good acceptance and minimal distraction from traffic. Reduced workload is thought to be brought about by helping the driver to maneuver, as he is only required to monitor proper functioning of the system. Workload was estimated by electrodermal activity recording while drivers tested five scenarios, involving or not the docking system. Results showed that docking precision was improved by the system, compared with manual docking. Drivers' workload was higher when they monitored the functioning of the system but was reduced after a learning process. Increased workload was evidenced in the event of dysfunction of the docking system, especially when drivers had to take over control. However, after habituation, such a system could be integrated into buses to improve safety during boarding and egress.

Assessing workload through physiological measurements in bus drivers using an automated system during docking.

The aim of the experiment was to test the effect of an automated system of bus docking on drivers' mental workload. Reduced workload is thought to be brought about by helping the driver to maneuver, as he or she is required only to monitor proper functioning of the system. However, the true impact of the system on drivers must be studied to guarantee good acceptance and minimal distraction from traffic. Workload was estimated by electrodermal activity recording while drivers tested 5 scenarios involving (or not involving) the docking system. Results showed that docking precision was improved when the system was used. When drivers monitored the functioning of the system, their workload was higher than that observed during manual docking; however, reduced workload was evidenced after a learning process. The docking system was also shown to increase workload in the event of dysfunction, especially when drivers had to take over control. Despite this particular situation, and after habituation, such a system could be integrated into buses to improve safety during boarding and egress.

Automatic Steering Based on Roadway Markers: From Highway Driving to Precision Docking

Bus Rapid Transit (BRT) is an effective alternative for providing rail-like corridor transit service. An advanced BRT concept involves the use of automated buses to provide functions of a rail transit system. A vehicle under automatic steering control following a prescribed trajectory is operated like a train on a rail. A lateral position sensing that uses roadway markers, such as magnetic markers embedded under the roadway, as lateral reference is one of the promising approaches for a reliable sensing system. The BRT concept requires the steering control system to consistently perform all necessary steering functions from high speed driving to low speed precision docking. This paper describes a single steering controller that achieves all performance objectives. Various data collected during several public demonstrations are presented in this paper to illustrate the effectiveness of the approach. These data include the following automatic steering control scenarios: over 100 mph high-speed driving, high-g maneuvers, sharp curve following, and low speed precision docking.

Multi-resolution contour-based fitting of macromolecular structures

A novel contour-based matching criterion is presented for the quantitative docking of high-resolution structures of components into low-resolution maps of macromolecular complexes. The proposed Laplacian filter is combined with a six-dimensional search using fast Fourier transforms to rapidly scan the rigid-body degrees of freedom of a probe molecule relative to a fixed target density map. A comparison of the docking performance with the standard cross-correlation criterion demonstrates that contour matching with the Laplacian filter significantly extends the viable resolution range of correlation-based fitting to resolutions as low as 30 Å. The gain in docking precision at medium to low resolution (15-30 Å) is critical for image reconstructions from electron microscopy (EM). The new algorithm enables for the first time the reliable docking of smaller molecular components into EM densities of large biomolecular assemblies at such low resolutions. As an example of the practical effectiveness of contour-based fitting, a new pseudo-atomic model of a microtubule was constructed from a 20 Å resolution EM map and from atomic structures of α and β tubulin subunits.

A docking system for microsatellites based onMEMS actuator arrays

Microelectromechanical system (MEMS) technology promises to improve performance of future spacecraft components while reducing mass, cost, and manufacturing time. Arrays of microcilia actuators offer a lightweight alternative to conventional docking systems for miniature satellites. Instead of mechanical guiding structures, such a system uses a surface tiled with MEMS cilia actuators to guide the satellite to its docking site.This paper summarizes work on an experimental system for precision docking of a `picosatellite' using MEMS cilia arrays. Microgravity is simulated with an aluminum puck on an airtable. A series of experiments is performed to characterize the cilia, with the goal of understanding the influence of normal force, picosatellite mass, docking velocity, cilia actuation frequency, interface material, and actuation strategy (`gait') on the performance of the MEMS docking system.We demonstrate a 4 cm2 cilia array capable of docking a41.2 g picosatellite with a 2 cm2 contact area withmicrometer precision. It is concluded that current MEMS ciliaarrays are effective in positioning and aligning miniature satellitesfor docking to a support satellite.

UsingSitusfor the registration of protein structures with low-resolution bead models from X-ray solution scattering

Three-dimensional bead models of proteins in solution are routinely determined from one-dimensional small-angle X-ray scattering (SAXS) data. TheSitussoftware provides a novel set of visualization and registration procedures to facilitate the localization of protein structures in low-resolution SAXS bead models. The docking algorithm takes advantage of a reduced representation of the input data sets by means of topology-representing neural networks to expedite the rigid-body search. The precision of the docking was tested on ten different simulated bead models: for &gt;100 beads typically arising in SAXS models, a docking precision of the order of an ångström can be achieved. The shape-matching score captured the correct solutions in all ten trial cases and was sufficiently stringent to yield unique matches in seven systems. A size-invariant shape descriptor of `sphericity' is proposed to assess the onset of ambiguity in the matching of globular molecules. The software, a tutorial and supplementary data are available at http://situs.scripps.edu/saxs.

Using Situs for Flexible and Rigid-Body Fitting of Multiresolution Single-Molecule Data

Wedescribe here a set of multiresolution visualization and docking procedures that we refer to as the Situs package. The package was developed to provide an efficient and robust method for the fitting of atomic structures into low-resolution data. The current release was optimized specifically for the visualization and docking of single molecules. A novel 3D graphics viewer, volslice3d, was developed for the package to provide an immersive virtual reality environment for measuring and rendering volumetric data sets. The precision of single-molecule, rigid-body docking was tested on simulated (noise-free) low-resolution density maps. For spatial resolutions near 20 Å typically arising in electron microscopy image reconstructions, a docking precision on the order of 1 Å can be achieved. The shape-matching score captured the correct solutions in all 10 trial cases and was sufficiently stringent to yield unique matches in 8 systems. Novel routines were developed for the flexible docking of atomic structures whose shape deviates from the corresponding low-resolution shape. Test calculations on isoforms of actin and lactoferrin demonstrate that the flexible docking faithfully reproduces conformational differences with a precision <2 Å if atomic structures are locally conserved.