Search NASA⌕ Search

SEARCH · Search NASA

Results for “computational docking”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Portability for GPU-accelerated molecular docking applications for cloud and HPC: can portable compiler directives provide performance across all platforms?

High-throughput structure-based screening of drug-like molecules has become a common tool in biomedical research. Recently, acceleration with graphics processing units (GPUs) has provided a large performance boost for molecular docking programs. Both cloud and high-performance computing (HPC) resources have been used for large screens with molecular docking programs; while NVIDIA GPUs have dominated cloud and HPC resources, new vendors such as AMD and Intel are now entering the field, creating the problem of software portability across different GPUs. Ideally, software productivity could be maximized with portable programming models that are able to maintain high performance across architectures. While in many cases compiler directives have been used as an easy way to offload parallel regions of a CPU-based program to a GPU accelerator, they may also be an attractive programming model for providing portability across different GPU vendors, in which case the porting process may proceed in the reverse direction: from low-level, architecture-specific code to higher-level directive-based abstractions. MiniMDock is a new mini-application (miniapp) designed to capture the essential computational kernels found in molecular docking calculations, such as are used in phar-maceutical drug discovery efforts, in order to test different solutions for porting across GPU architectures. Here we extend MiniMDock to GPU offloading with OpenMP directives, and compare to performance of kernels using CUDA and HIP on NVIDIA and AMD GPUs, respectively, as well as across different compilers, exploring performance bottlenecks. We document this reverse-porting process, from highly optimized device code to a higher-level version using directives, compare code structure, and describe barriers that were overcome in this effort.

Thavappiragasam, Mathialakan↗
NASA NTRS1974

Six degree of freedom FORTRAN program, ASTP docking dynamics, users guide

The digital program ASTP Docking Dynamics as outlined is intended to aid the engineer using the program to determine the docking system loads and attendant vehicular motion resulting from docking two vehicles that have an androgynous, six-hydraulic-attenuator, guide ring, docking interface similar to that designed for the Apollo/Soyuz Test Project (ASTP). This program is set up to analyze two different vehicle combinations: the Apollo CSM docking to Soyuz and the shuttle orbiter docking to another orbiter. The subroutine modifies the vehicle control systems to describe one or the other vehicle combinations; the rest of the vehicle characteristics are changed by input data. To date, the program has been used to predict and correlate ASTP docking loads and performance with docking test program results from dynamic testing. The program modified for use on IBM 360 computers. Parts of the original docking system equations in the areas of hydraulic damping and capture latches are modified to better describe the detail design of the ASTP docking system.

Mount, G. O., Jr.↗
DOE OSTI2025

Unraveling the Hsp70-ROS-autophagy axis in pentachlorophenol-challenged lung and liver epithelial cells

Pentachlorophenol (PCP) was extensively utilized as an organochlorine pesticide and wood preservative in the United States from the 1930s until the Environmental Protection Agency (EPA) imposed restrictions due to concerns about its toxicity and potential carcinogenic properties. Although it is no longer widely used, PCP remains a concern due to its environmental persistence and potential for long-term health effects. Significant occupational and environmental exposures have likely occurred, with the health and economic costs of PCP exposure potentially being substantial given its known toxicity. Notably, PCP exhibits rapid absorption through both the skin and respiratory system and has been shown to cause hepatotoxicity, developmental toxicity, immunotoxicity, irritation, and carcinogenicity in laboratory animal studies. PCP exposure induces oxidative stress, a key mechanism underlying its inflammatory and toxic effects, which can activate cellular stress responses including upregulation of heat shock protein 70 (Hsp70). Previous studies in lung and liver epithelial cells have shown that Hsp70 and oxidative stress play pivotal roles in triggering autophagy. This study establishes the critical role of the Hsp70-reactive oxygen species (ROS)-autophagy axis in regulating cellular responses to PCP exposure in human alveolar (A549) and liver carcinoma (HepG2) epithelial cells. Our research elucidated the molecular mechanisms underlying PCP's cellular effects, demonstrating that its exposure resulted in increased expression of autophagy-related proteins (Beclin-1, LC3B, ATG12, and ATG16), subunits of NADPH oxidase (NCF-1, NCF-2, NOX2, and Rac), and antioxidant proteins (SOD and GPx) in both lung and liver cell types. Notably, PCP augmented the interaction between Hsp70 and the autophagy regulator Beclin-1. Pretreatment with the ROS inhibitor N-acetylcysteine or Hsp70 knockdown markedly reversed PCP-induced responses. Our in-silico protein–protein docking analysis and molecular dynamics simulation studies revealed enhanced interactions and/or stable confirmations maintained throughout the simulations for TLR4-Hsp70 and Hsp70-Beclin-1 complexes in the presence of PCP. These findings provide a strong foundation for future studies, employing in vivo experimental models and human populations to identify promising targets for PCP-induced toxicity and cellular injury. As a result, these findings may have far-reaching implications for public health and environmental policy, ultimately leading to the identification of biomarkers and the development of more effective interventions for environmentally induced toxicity and diseases.

97 MATHEMATICS AND COMPUTING↗
NASA NTRS2011

POSE Algorithms for Automated Docking

POSE (relative position and attitude) can be computed in many different ways. Given a sensor that measures bearing to a finite number of spots corresponding to known features (such as a target) of a spacecraft, a number of different algorithms can be used to compute the POSE. NASA has sponsored the development of a flash LIDAR proximity sensor called the Vision Navigation Sensor (VNS) for use by the Orion capsule in future docking missions. This sensor generates data that can be used by a variety of algorithms to compute POSE solutions inside of 15 meters, including at the critical docking range of approximately 1-2 meters. Previously NASA participated in a DARPA program called Orbital Express that achieved the first automated docking for the American space program. During this mission a large set of high quality mated sensor data was obtained at what is essentially the docking distance. This data set is perhaps the most accurate truth data in existence for docking proximity sensors in orbit. In this paper, the flight data from Orbital Express is used to test POSE algorithms at 1.22 meters range. Two different POSE algorithms are tested for two different Fields-of-View (FOVs) and two different pixel noise levels. The results of the analysis are used to predict future performance of the POSE algorithms with VNS data.

Heaton, Andrew F.↗
DOE OSTI2021

Hotspot Coevolution Is a Key Identifier of Near-Native Protein Complexes

Protein–protein interactions play a key role in mediating numerous biological functions, with more than half the proteins in living organisms existing as either homo- or hetero-oligomeric assemblies. Protein subunits that form oligomers minimize the free energy of the complex, but exhaustive computational search-based docking methods have not comprehensively addressed the challenge of distinguishing a natively bound complex from non-native forms. Current protein docking approaches address this problem by sampling multiple binding modes in proteins and scoring each mode, with the lowest-energy (or highest scoring) binding mode being regarded as a near-native complex. However, high-scoring modes often match poorly with the true bound form, suggesting a need for improvement of the scoring function. Here in this study, we propose a scoring function, KFC-E, that accounts for both conservation and coevolution of putative binding hotspot residues at protein–protein interfaces. We tested KFC-E on four benchmark sets of unbound examples and two benchmark sets of bound examples, with the results demonstrating a clear improvement over scores that examine conservation and coevolution across the entire interface.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Structure-Based Design of Small-Molecule Inhibitors of Human Interleukin-6

Human Interleukin-6 (hIL-6) is a pro inflammatory cytokine that binds to its receptor, IL-6Rα followed by binding to gp130 and subsequent dimerization to form a hexamer signaling complex. As a critical inflammation mediator, hIL-6 is associated with a diverse range of diseases and monoclonal antibodies in clinical use that either target IL-6Rα or hIL-6 to inhibit signaling. Here, we perform high-throughput structure-based computational screening using ensemble docking for small-molecule antagonists for which the target conformations were taken from 600 ns long molecular dynamics simulations of the apo protein. Prior knowledge of the contact sites from binary complex studies and experimental work was incorporated into the docking studies. The top 20 scoring ligands from the in silico studies after post analysis were subjected to in vitro functional assays. Among these compounds, the ligand with the second-highest calculated binding affinity experimentally showed an ~84% inhibitory effect on IL6-induced STAT3 reporter activity at 10 μM concentration. This finding may pave the way for designing small-molecule inhibitors of hIL-6 of therapeutic significance.

Human Interleukin-6↗
NASA NTRS1978

Large space structures assembly simulation

Simulation requirements for the evaluation of Large Space Structure assembly techniques have been developed by analysis of a typical large space structure through its entire life cycle. Applications of neutral buoyancy, air bearing simulators, computer driven rendezvous and docking simulators, and other simulation modes were studied. Several demonstrations of assembly techniques in neutral buoyancy have been conducted at MSFC using large scale hardware. Experience from those demonstrations and subsequent simulations can be used to select viable approaches for orbital application in operational vehicles. Demonstration results are presented which illustrate techniques and hardware designs that can significantly simplify construction of early large space structures.

Hall, S. B.↗
NASA NTRS2003

Laser-Based Relative Navigation and Guidance for Space Shuttle Proximity Operations

American manned spacecraft have used visual piloting techniques in the terminal phase of randezvous during the Gemini, Apollo, Skylab, and Space Shuttle programs. In the last several years, space- shuttle astronauts have used the Rendezvous and Proximity Operations Program (RPOP), running; on a laptop computer, as a guidance and navigation aid during proximity operations. By processing measurements to the target satellite taken by a laser sensor, RPOP provides the shuttle crew with a more accurate relative position and velocity than from any other source. The inclusion of guidance algorithms allows RPOP to determine delta-velocities to fly very efficient, repeatable trajectories. This paper will focus on the guidance and navigation algorithms in RPOP, as well as results from simulation and flight. Although developed for shuttle proximity operations, the RPOP algorithms have potential applicability to an automated vehicle.

Laser sensors↗
DOE OSTI2025

Protein-ligand binding affinity prediction using multi-instance learning with docking structures

Recent advances in 3D structure-based deep learning approaches demonstrate improved accuracy in predicting protein-ligand binding affinity in drug discovery. These methods complement physics-based computational modeling such as molecular docking for virtual high-throughput screening. Despite recent advances and improved predictive performance, most methods in this category primarily rely on utilizing co-crystal complex structures and experimentally measured binding affinities as both input and output data for model training. Nevertheless, co-crystal complex structures are not readily available and the inaccurate predicted structures from molecular docking can degrade the accuracy of the machine learning methods. We introduce a novel structure-based inference method utilizing multiple molecular docking poses for each complex entity. Our proposed method employs multi-instance learning with an attention network to predict binding affinity from a collection of docking poses. We validate our method using multiple datasets, including PDBbind and compounds targeting the main protease of SARS-CoV-2. The results demonstrate that our method leveraging docking poses is competitive with other state-of-the-art inference models that depend on co-crystal structures. This method offers binding affinity prediction without requiring co-crystal structures, thereby increasing its applicability to protein targets lacking such data.

97 MATHEMATICS AND COMPUTING↗
NASA NTRS1982

Development of an autonomous video rendezous and docking system

Video control systems using three flashing lights and two other types of docking aids were evaluated through computer simulation and other approaches. The three light system performed much better than the others. Its accuracy is affected little by tumbling of the target spacecraft, and in the simulations it was able to cope with attitude rates up to 20,000 degrees per hour about the docking axis. Its performance with rotation about other axes is determined primarily by the state estimation and goal setting portions of the control system, not by measurement accuracy. A suitable control system, and a computer program that can serve as the basis for the physical simulation are discussed.

Tietz, J. C.↗
NASA NTRS1974

Space tug automatic docking control study. LOCDOK users manual

A users's manual for the computer programs involved in a study of the space tug docking simulation is presented. The following subjects are considered: (1) subroutine narratives, (2) program elements, (3) system subroutines, and (4) Univac 1108 cross reference listing. The functional and operational requirements for the computer programming are explained.

Source record↗
NASA NTRS1992

Application of fuzzy logic-neural network based reinforcement learning to proximity and docking operations

As part of the Research Institute for Computing and Information Systems (RICIS) activity, the reinforcement learning techniques developed at Ames Research Center are being applied to proximity and docking operations using the Shuttle and Solar Max satellite simulation. This activity is carried out in the software technology laboratory utilizing the Orbital Operations Simulator (OOS). This interim report provides the status of the project and outlines the future plans.

Jani, Yashvant↗
DOE OSTI2022

BIPSPI+: Mining Type-Specific Datasets of Protein Complexes to Improve Protein Binding Site Prediction

Computational approaches for predicting protein-protein interfaces are extremely useful for understanding and modelling the quaternary structure of protein assemblies. In particular, partner-specific binding site prediction methods allow delineating the specific residues that compose the interface of protein complexes. In recent years, new machine learning and other algorithmic approaches have been proposed to solve this problem. However, little effort has been made in finding better training datasets to improve the performance of these methods. With the aim of vindicating the importance of the training set compilation procedure, in this work we present BIPSPI+, a new version of our original server trained on carefully curated datasets that outperforms our original predictor. We show how prediction performance can be improved by selecting specific datasets that better describe particular types of protein interactions and interfaces (e.g. homo/hetero). In addition, our upgraded web server offers a new set of functionalities such as the sequence-structure prediction mode, hetero- or homo-complex specialization and the guided docking tool that allows to compute 3D quaternary structure poses using the predicted interfaces. BIPSPI+ is freely available at https://bipspi.cnb.csic.es.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

SAXS analysis of the intrinsic tenase complex bound to a lipid nanodisc highlights intermolecular contacts between factors VIIIa/IXa

Abstract The intrinsic tenase (Xase) complex, formed by factors (f) VIIIa and fIXa, forms on activated platelet surfaces and catalyzes the activation of factor X to Xa, stimulating thrombin production in the blood coagulation cascade. The structural organization of the membrane-bound Xase complex remains largely unknown, hindering our understanding of the structural underpinnings that guide Xase complex assembly. Here, we aimed to characterize the Xase complex bound to a lipid nanodisc with biolayer interferometry (BLI), Michaelis–Menten kinetics, and small-angle X-ray scattering (SAXS). Using immobilized lipid nanodiscs, we measured binding rates and nanomolar affinities for fVIIIa, fIXa, and the Xase complex. Enzyme kinetic measurements demonstrated the assembly of an active enzyme complex in the presence of lipid nanodiscs. An ab initio molecular envelope of the nanodisc-bound Xase complex allowed us to computationally model fVIIIa and fIXa docked onto a flexible lipid membrane and identify protein–protein interactions. Our results highlight multiple points of contact between fVIIIa and fIXa, including a novel interaction with fIXa at the fVIIIa A1–A3 domain interface. Lastly, we identified hemophilia A/B-related mutations with varying severities at the fVIIIa/fIXa interface that may regulate Xase complex assembly. Together, our results support the use of SAXS as an emergent tool to investigate the membrane-bound Xase complex and illustrate how mutations at the fVIIIa/fIXa dimer interface may disrupt or stabilize the activated enzyme complex.

Hematology↗
NASA NTRS1971

Space shuttle vehicle automatic docking study

The material presented is divided into three main areas of accomplishment. The first is a description of the angle only docking sensor concept and the computational requirements to develop useful guidance information from the raw angle only data. The second describes the analytical effort including the MIT in-house computer simulation, the development of guidance equations and vehicle stability related thereto, and presents the results of studies covering the effects of employing Kalman filtering with the sensor. The third area presents the conclusions and recommendations resulting from the program. Much of the material has appeared in previous reports, but is included here for the sake of completeness. New material indicating how the computer might operate to identify the individual sources in the target array is included.

Blanchard, E. P.↗
NASA NTRS1972

Study on propellant dynamics during docking

The marker-and-cell numerical technique was applied to the study of axisymmetric and two-dimensional flow of liquid in containers under low gravity conditions. The purpose of the study was to provide the capability for numerically simulating liquid propellant motion in partially filled containers during a docking maneuver in orbit. A computer program to provide this capability for axisymmetric and two-dimensional flow was completed and computations were made for a number of hypothetical flow conditions.

Feng, G. C.↗
NASA NTRS1986

Pseudo-prototyping of aerospace mechanical dynamic systems with a generalized computer program

The ADAMS computer program for automated analysis of mechanisms and machines is described. The program automatically formulates mathematical models for prototype or existing mechanisms with the minimum necessary physical and geometric data. The model can then be analyzed in various modes of analysis. The outputs (displacements, velocities, acceleration and forces) can be produced in tabular and graphical (plots, wire frame graphics) form. The application of this computer program to simulating satellite docking maneuvers is illustrated.

Sohoni, Vikram N.↗