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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.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2015

Protein structure prediction guided by crosslinking restraints – A systematic evaluation of the impact of the crosslinking spacer length

Recent development of high-resolution mass spectrometry (MS) instruments enables chemical crosslinking (XL) to become a high-throughput method for obtaining structural information about proteins. Restraints derived from XL-MS experiments have been used successfully for structure refinement and protein–protein docking. However, one formidable question is under which circumstances XL-MS data might be sufficient to determine a protein’s tertiary structure de novo? Answering this question will not only include understanding the impact of XL-MS data on sampling and scoring within a de novo protein structure prediction algorithm, it must also determine an optimal crosslinker type and length for protein structure determination. While a longer crosslinker will yield more restraints, the value of each restraint for protein structure prediction decreases as the restraint is consistent with a larger conformational space. In this study, the number of crosslinks and their discriminative power was systematically analyzed in silico on a set of 2055 non-redundant protein folds considering Lys–Lys, Lys–Asp, Lys–Glu, Cys–Cys, and Arg–Arg reactive crosslinkers between 1 and 60 Å. Depending on the protein size a heuristic was developed that determines the optimal crosslinker length. Next, simulated restraints of variable length were used to de novo predict the tertiary structure of fifteen proteins using the BCL::Fold algorithm. The results demonstrate that a distinct crosslinker length exists for which information content for de novo protein structure prediction is maximized. The sampling accuracy improves on average by 1.0 Å and up to 2.2 Å in the most prominent example. XL-MS restraints enable consistently an improved selection of native-like models with an average enrichment of 2.1.

Biochemistry & Molecular Biology↗
DOE OSTI2016

Pushing the size limit of de novo structure ensemble prediction guided by sparse SDSL-EPR restraints to 200 residues: The monomeric and homodimeric forms of BAX

Structure determination remains a challenge for many biologically important proteins. In particular, proteins that adopt multiple conformations often evade crystallization in all biologically relevant states. Although computational de novo protein folding approaches often sample biologically relevant conformations, the selection of the most accurate model for different functional states remains a formidable challenge, in particular, for proteins with more than about 150 residues. Electron paramagnetic resonance (EPR) spectroscopy can obtain limited structural information for proteins in well-defined biological states and thereby assist in selecting biologically relevant conformations. The present study demonstrates that de novo folding methods are able to accurately sample the folds of 192-residue long soluble monomeric Bcl-2-associated X protein (BAX). The tertiary structures of the monomeric and homodimeric forms of BAX were predicted using the primary structure as well as 25 and 11 EPR distance restraints, respectively. The predicted models were subsequently compared to respective NMR/X-ray structures of BAX. EPR restraints improve the protein-size normalized root-mean-square-deviation (RMSD100) of the most accurate models with respect to the NMR/crystal structure from 5.9 Å to 3.9 Å and from 5.7 Å to 3.3 Å, respectively. Additionally, the model discrimination is improved, which is demonstrated by an improvement of the enrichment from 5% to 15% and from 13% to 21%, respectively.

Biochemistry & Molecular Biology↗
NASA NTRS2004

Multipurpose Crew Restraints for Long Duration Space Flights

With permanent human presence onboard the International Space Station (ISS), a crew will be living and working in microgravity, interfacing with their physical environment. Without optimum restraints and mobility aids (R&MA' s), the crewmembers may be handicapped for perfonning some of the on-orbit tasks. In addition to weightlessness, the confined nature of a spacecraft environment results in ergonomic challenges such as limited visibility and access to the activity area and may cause prolonged periods of unnatural postures. Thus, determining the right set of human factors requirements and providing an ergonomically designed environment are crucial to astronauts' well-being and productivity. The purpose of this project is to develop requirements and guidelines, and conceptual designs, for an ergonomically designed multi-purpose crew restraint. In order to achieve this goal, the project would involve development of functional and human factors requirements, design concept prototype development, analytical and computer modeling evaluations of concepts, two sets of micro gravity evaluations and preparation of an implementation plan. It is anticipated that developing functional and design requirements for a multi-purpose restraint would facilitate development of ergonomically designed restraints to accommodate the off-nominal but repetitive tasks, and minimize the performance degradation due to lack of optimum setup for onboard task performance. In addition, development of an ergonomically designed restraint concept prototype would allow verification and validation of the requirements defined. To date, we have identified "unique" tasks and areas of need, determine characteristics of "ideal" restraints, and solicit ideas for restraint and mobility aid concepts. Focus group meetings with representatives from training, safety, crew, human factors, engineering, payload developers, and analog environment representatives were key to assist in the development of a restraint concept based on previous flight experiences, the needs of future tasks, and crewmembers' preferences. Also, a catalog with existing IVA/EVA restraint and mobility aids has been developed. Other efforts included the ISS crew debrief data on restraints, compilation of data from MIR, Skylab and ISS on restraints, and investigating possibility of an in-flight evaluation of current restraint systems. Preliminary restraint concepts were developed and presented to long duration crewmembers and focus groups for feedback. Currently, a selection criterion is being refined for prioritizing the candidate concepts. Next steps include analytical and computer modeling evaluations of the selected candidate concepts, prototype development, and microgravity evaluations.

Whitmore, Mihriban↗
NASA NTRS1995

Evaluation of restraint system concepts for the Japanese Experiment Module flight demonstration

The current International Space Station configuration includes a Japanese Experiment Module which relies on a large manipulator and a smaller dexterous manipulator to operate outside the pressurized environment of the experiment module. The module's flight demonstration is a payload that will be mounted in the aft flight deck on STS-87 to evaluate a prototype of the dexterous manipulator. Since the payload operations entail two 8-hour scenarios on consecutive days, adequate operator restraint at the workstation will be critical to the perceived success or failure of the payload. Simulations in reduced gravity environment on the KC-135A were the only way to evaluate the restraint systems and workstation configuration. Two astronaut and two non-astronaut operators evaluated the Advanced Lower Body Extremities Restraint Test and a foot loop restraint system by performing representative tasks at the workstation in each of the two restraint systems; at the end of each flight they gave their impressions of each system and the workstation. Results indicated that access to the workstation switch panels was difficult and manipulation of the hand controllers forced operators too low for optimal viewing of the aft flight deck monitors. The workstation panel should be angled for better visibility, and infrequently used switches should be on the aft flight deck panel. Pitch angle and placement of the hand controllers should optimize the operator's eye position with respect to the monitors. The lower body restraint was preferred over the foot loops because it allowed operators to maintain a more relaxed posture during long-duration tasks, its height adjustability allowed better viewing of aft flight deck monitors, and it provided better restraint for reacting forces imparted on the operator at the workstation. The foot loops provide adequate restraint for the flight demonstration tasks identified. Since results will impact the design of the workstation, both restraints should be flown and used during operation of the flight demonstration payload to evaluate the effect of restraint during long-duration tasks.

Sampaio, Carlos E.↗
NASA NTRS2005

International Space Station Crew Restraint Design

With permanent human presence onboard the International Space Station (ISS), crews will be living and working in microgravity, dealing with the challenges of a weightless environment. In addition, the confined nature of the spacecraft environment results in ergonomic challenges such as limited visibility and access to the activity areas, as well as prolonged periods of unnatural postures. Without optimum restraints, crewmembers may be handicapped for performing some of the on-orbit tasks. Currently, many of the tasks on ISS are performed with the crew restrained merely by hooking their arms or toes around handrails to steady themselves. This is adequate for some tasks, but not all. There have been some reports of discomfort/calluses on the top of the toes. In addition, this type of restraint is simply insufficient for tasks that require a large degree of stability. Glovebox design is a good example of a confined workstation concept requiring stability for successful use. They are widely used in industry, university, and government laboratories, as well as in the space environment, and are known to cause postural limitations and visual restrictions. Although there are numerous guidelines pertaining to ventilation, seals, and glove attachment, most of the data have been gathered in a 1-g environment, or are from studies that were conducted prior to the early 1980 s. Little is known about how best to restrain a crewmember using a glovebox in microgravity. In 2004, The Usability Testing and Analysis Facility (UTAF) at the NASA Johnson Space Center completed development/evaluation of several design concepts for crew restraints to meet the various needs outlined above. Restraints were designed for general purpose use, for teleoperation (Robonaut) and for use with the Life Sciences Glovebox. All design efforts followed a human factors engineering design lifecycle, beginning with identification of requirements followed by an iterative prototype/test cycle. Anthropometric modeling was completed for the 5th percentile Asian female and the 95th percentile American male for all restraints. A series of three evaluations was performed onboard NASA's reduced gravity aircraft (KC-135). For all evaluations, participants performed representative tasks while being videotaped, and then completed a questionnaire following each flight day. The questionnaire included ratings scales and free format questions to assess topics such as comfort, stability provided, flexibility provided, etc. Results from the three flight evaluations are being used to develop the human factors design requirements for crew restraint concepts for 1) general purpose restraints, 2) teleoperation restraints and 3) glovebox restraints. The poster presentation will describe the detailed methodology used, results from each of the three evaluations, and the resulting human factors recommendations for the design of these restraints.

Whitmore, M.↗
DOE OSTI2026

Validated ligand geometries for macromolecular refinement restraints and molecular-mechanics force fields

In macromolecular structure refinement, the low observation-to-parameter ratio and the lack of high-resolution data are countered by using a priori information in the form of restraints. Having accurate geometries of the chemical entities in the sample is paramount for generating accurate chemical restraints and, therefore, accurate macromolecular structures. In particular, it is desirable to have accurate restraints for known and novel ligand entities. Quantum mechanics (QM) can minimize the energy of a ligand by adjusting its geometry, and these geometries can be used to generate restraints for macromolecular refinement. This article describes a library of approximately 37 000 small molecules extracted from the Chemical Component Dictionary in the Protein Data Bank and minimized by density-functional QM. The library includes restraint files for use in crystallography or cryo-EM refinement, along with files suitable for molecular-dynamics simulation. Because the geometries are validated using the Cambridge Structural Database, the restraints library provides users with both functional restraints and minimized geometries. This work also provides procedures for generating new and accurate restraints.

Amber↗
NASA NTRS1994

Use of a pitch adjustable foot restraint system: Operator strength capability and load requirements

The zero-gravity environment creates a need for a proper human body restraint system to maintain a comfortable posture with less fatigue and to maximize productivity. In addition, restraint systems must be able to meet the loading demands of maintenance and assembly tasks performed on orbit. The shuttle's primary intravehicular astronaut restraint system is currently a foot loop design that attaches to flat surfaces on the shuttle, allowing for varying mounting locations and easy egress and ingress. However, this design does not allow for elevation, pitch, or foot loop length adjustment. Several prototype foot restraint systems are being evaluated for use aboard the space station and the space shuttle. The JSC Anthropometry and Biomechanics Laboratory initiated this study to quantify the maximum axial forces and moments that would be induced on a foot loop type of restraint while operators performed a torque wrench task, also allowing for angling the restraint pitch angle to study yet another effect. Results indicate that the greatest forces into the torque wrench and into the foot restraint system occur while the operator performs an upward effort. This study did not see any significant difference in the operators' force due to pitch orientation. Thus, in a work environment in which hand holds are available, no significant influence of the pitch angle on forces imparted to the restraint system existed.

Wilmington, Robert P.↗
DOE OSTI2017

An editor for the generation and customization of geometry restraints

Chemical restraints for use in macromolecular structure refinement are produced by a variety of methods, including a number of programs that use chemical information to generate the required bond, angle, dihedral, chiral and planar restraints. These programs help to automate the process and therefore minimize the errors that could otherwise occur if it were performed manually. Furthermore, restraint-dictionary generation programs can incorporate chemical and other prior knowledge to provide reasonable choices of types and values. However, the use of restraints to define the geometry of a molecule is an approximation introduced with efficiency in mind. The representation of a bond as a parabolic function is a convenience and does not reflect the true variability in even the simplest of molecules. Another complicating factor is the interplay of the molecule with other parts of the macromolecular model. Finally, difficult situations arise from molecules with rare or unusual moieties that may not have their conformational space fully explored. These factors give rise to the need for an interactive editor for WYSIWYG interactions with the restraints and molecule. Restraints Editor, Especially Ligands (REEL) is a graphical user interface for simple and error-free editing along with additional features to provide greater control of the restraint dictionaries in macromolecular refinement.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1997

Urinary excretion of cortisol from rhesus monkeys (Macaca mulatta) habituated to restraint

Use of monkeys in research has often required that they be restrained in a chair. However, chair restraint can elicit an initial neuroendocrine stress response. Also, inactivity associated with restraint can induce muscular atrophy. We proposed that prior habituation of monkeys to chair restraint would attenuate these neuroendocrine responses without causing substantial muscle wasting. Four rhesus monkeys (Macaca mulatta) were trained and habituated to a restraint chair specifically designed for spaceflight. During the study, monkeys were placed in metabolic cages for 7 days (prerestraint, Phase I), placed in a chair restraint for 18 days (Phase II), and then returned to their metabolic cages for 5 days (postrestraint, Phase III). Urine was collected between 0700-1100 daily, and measurements of cortisol, creatinine, and electrolyte concentrations were adjusted for hourly excretion rates. Body weights of the monkeys did not change between start of the prerestraint and postrestraint phases (10.3 +/- 0.8 vs. 10.3 +/- 0.9 kg, respectively). During the 3 phases, mean excretion rate of cortisol did not change (24.1 +/- 10.3, 26.7 +/- 7.7, and 19.3 +/- 5.8 microg/h, respectively). Mean excretion rate of creatinine (37.3 +/- 7.5, 37.5 +/- 12.2, and 36.9 +/- 17.1 mg/h, respectively), Na+ (3.3 +/- 1.2, 3.2 +/- 1.2, 2.2 +/- 1.8 mmol/h, respectively), and K+ (5.3 +/- 1.8, 5.4 +/- 1.6, and 4.3 +/- 2.8 mmol/h, respectively) were also not altered. Lack of an increase in excreted urinary cortisol suggested that prior habituation to chair restraint attenuated neuroendocrine responses reported previously. Also, the chair restraint method used appeared to allow adequate activity, because the monkeys did not have indices of muscle wasting.

NASA Center ARC↗
NASA NTRS2004

Special Purpose Crew Restraints for Teleoperation

With permanent human presence onboard the International Space Station (ISS), and long duration space missions being planned for the moon and Mars, humans will be living and working in microgravity over increasingly long periods of time. In addition to weightlessness, the confined nature of a spacecraft environment results in ergonomic challenges such as limited visibility, and access to the activity area. These challenges can result in prolonged periods of unnatural postures for the crew, ultimately causing pain, injury, and loss of productivity. Determining the right set of human factors requirements and providing an ergonomically designed environment is crucial to mission success. While a number of general purpose restraints have been used on ISS (handrails, foot loops), experience has shown that these general purpose restraints may not be optimal, or even acceptable for some tasks that have unique requirements. For example, some onboard activities require extreme stability (e.g., glovebox microsurgery), and others involve the use of arm, torso and foot movements in order to perform the task (e-g. robotic teleoperation); standard restraint systems will not work in these situations. The Usability Testing and Analysis Facility (WAF) at the NASA Johnson Space Center began evaluations of crew restraints for these special situations by looking at NASAs Robonaut. Developed by the Robot Systems Technology Branch, Robonaut is a humanoid robot that can be remotely operated through a tetepresence control system by an operator. It was designed to perform work in hazardous environments (e.g., Extra Vehicular Activities). A Robonaut restraint was designed, modeled for the population, and ultimately tested onboard the KC-135 microgravity aircraft. While in microgravity, participants were asked to get in and out of the restraint from different locations, perform maximum reach exercises, and finally to teleoperate Robonaut while in the restraint. The sessions were videotaped, and participants completed a questionnaire at the end of each flight day. Results from this evaluation are being used to develop the human factors design requirements for teleoperation tasks in microgravity.

Whitmore, Mihriban↗
DOE OSTI2023

In situ ligand restraints from quantum-mechanical methods

In macromolecular crystallographic structure refinement, ligands present challenges for the generation of geometric restraints due to their large chemical variability, their possible novel nature and their specific interaction with the binding pocket of the protein. Quantum-mechanical approaches are useful for providing accurate ligand geometries, but can be plagued by the number of minima in flexible molecules. In an effort to avoid these issues, the Quantum Mechanical Restraints (QMR) procedure optimizes the ligand geometry in situ , thus accounting for the influence of the macromolecule on the local energy minima of the ligand. The optimized ligand geometry is used to generate target values for geometric restraints during the crystallographic refinement. As demonstrated using a sample of >2330 ligand instances in >1700 protein–ligand models, QMR restraints generally result in lower deviations from the target stereochemistry compared with conventionally generated restraints. In particular, the QMR approach provides accurate torsion restraints for ligands and other entities.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Introduction of a bounded penalty function in contact‐assisted simulations of protein structures to omit false restraints

Contact‐assisted simulations, the contacts being predicted or determined experimentally, have become very important in the determination of the structures of proteins and other biological macromolecules. In this work, the effect of contact‐distance restraints on the simulated structures was investigated with the use of multiplexed replica exchange simulations with the coarse‐grained UNRES force field. A modified bounded flat‐bottom restraint function that does not generate a gradient when a restraint cannot be satisfied was implemented. Calculations were run with (i) a set of four small proteins, with contact restraints derived from experimental structures, and (ii) selected CASP11 and CASP12 targets, with restraints as used at prediction time. The bounded penalty function largely omitted false contacts, which were usually inconsistent. It was found that at least 20% of correct contacts must be present in the restraint set to improve model quality with respect to unrestrained simulations. © 2019 Wiley Periodicals, Inc.

Lubecka, Emilia A.↗
NASA NTRS1963

Optimizations of Human Restraint Systems for Short-Period Acceleration

A restraint system's main function is to restrain its occupant when his vehicle is subjected to acceleration. If the restraint system is rigid and well-fitting (to eliminate slack) then it will transmit the vehicle acceleration to its occupant without modifying it in any way. Few present-day restraint systems are stiff enough to give this one-to-one transmission characteristic, and depending upon their dynamic characteristics and the nature of the vehicle's acceleration-time history, they will either magnify or attenuate the acceleration. Obviously an optimum restraint system will give maximum attenuation of an input acceleration. In the general case of an arbitrary acceleration input, a computer must be used to determine the optimum dynamic characteristics for the restraint system. Analytical solutions can be obtained for certain simple cases, however, and these cases are considered in this paper, after the concept of dynamic models of the human body is introduced. The paper concludes with a description of an analog computer specially developed for the Air Force to handle completely general mechanical restraint optimization programs of this type, where the acceleration input may be any arbitrary function of time.

Payne, P. R.↗
NASA NTRS1999

Microgravity Workstation and Restraint Evaluations

Confined workstations, where the operator has limited visibility and physical access to the work area, may cause prolonged periods of unnatural posture. Impacts on performance, in terms of fatigue and posture, may occur especially if the task is tedious and repetitive or requires static muscle loading. The glovebox design is a good example of the confined workstation concept. Within the scope of the 'Microgravity Workstation and Restraint Evaluation' project, funded by the NASA Headquarters Life Sciences Division, it was proposed to conduct a series of evaluations in ground, KC-135 and Shuttle environments to investigate the human factors issues concerning confined/unique workstations, such as gloveboxes, and also including crew restraint requirements. As part of the proposed integrated evaluations, two Shuttle Detailed Supplementary Objectives (DSOs) were manifested; one on Space Transportation System (STS)-90 and one on STS-88. The DSO on STS-90 evaluated use of the General Purpose Workstation (GPWS). The STS-88 mission was planned to evaluate a restraint system at the Remote Manipulator System (RMS). In addition, KC- 1 35 flights were conducted to investigate user/workstation/restraint integration for long-duration microgravity use. The scope of these evaluations included workstations and restraints to be utilized in the ISS environment, but also incorporated other workstations/ restraints in an attempt to provide findings/requirements with broader applications across multiple programs (e.g., Shuttle, ISS, and future Lunar-Mars programs). In addition, a comprehensive electronic questionnaire has been prepared and is under review by the Astronaut Office which will compile crewmembers' lessons learned information concerning glovebox and restraint use following their missions. These evaluations were intended to be complementary and were coordinated with hardware developers, users (crewmembers), and researchers. This report is intended to provide a summary of the findings from each of the evaluations.

Chmielewski, C.↗
NASA NTRS1999

Ergonomic Evaluation of the Foot Restraint Equipment Device (FRED)

Within the scope of the Microgravity Workstation and Restraint Evaluation project, funded by the NASA Headquarters Life Sciences Division, evaluations were proposed to be conducted in ground, KC-135, and/or Shuttle environments to investigate the human factors engineering (HFE) issues concerning confined/unique workstations, including crew restraint requirements. As part of these evaluations, KC-135 flights were conducted to investigate user/ workstation/ restraint integration for microgravity use of the FRED with the RMS workstation. This evaluation was a pre-cursor to Detailed Supplementary Objective (DSO) - 904 on STS-88. On that mission, a small-statured astronaut will be using the FRED restraint while working at the Aft RMS workstation. The DSO will collect video for later posture analyses, as well as subjective data in the form of an electronic questionnaire. This report describes the current FRED KC-135 evaluations. The primary objectives were to evaluate the usability of the FRED and to verify the DSO in-flight setup. The restraint interface evaluation consisted of four basic areas of restraint use: 1) adjustability; 2) general usability and comfort; 3) usability at the RMS workstation; and 4) assembly and disassembly.

Whitmore, Mihriban↗
DOE OSTI2020

Arginine off-kilter: guanidinium is not as planar as restraints denote

Crystallographic refinement of macromolecular structures relies on stereochemical restraints to mitigate the typically poor data-to-parameter ratio. For proteins, each amino acid has a unique set of geometry restraints which represent stereochemical information such as bond lengths, valence angles, torsion angles, dihedrals and planes. It has been shown that the geometry in refined structures can differ significantly from that present in libraries; for example, it was recently reported that the guanidinium moiety in arginine is not symmetric. In this work, the asymmetry of the N ∊ —C ζ —N η1 and N ∊ —C ζ —N η2 valence angles in the guanidinium moiety is confirmed. In addition, it was found that the C δ atom can deviate significantly (more than 20°) from the guanidinium plane. This requires the relaxation of the planar restraint for the C δ atom, as it otherwise causes the other atoms in the group to compensate by distorting the guanidinium core plane. A new set of restraints for the arginine side chain have therefore been formulated, and are available in the software package Phenix , that take into account the asymmetry of the group and the planar deviation of the C δ atom. This is an example of the need to regularly revisit the geometric restraint libraries used in macromolecular refinement so that they reflect the best knowledge of the structural chemistry of their components available at the time.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2019

Improved chemistry restraints for crystallographic refinement by integrating the Amber force field into Phenix

The refinement of biomolecular crystallographic models relies on geometric restraints to help address the paucity of experimental data typical in these experiments. Limitations in these restraints can degrade the quality of the resulting atomic models. Here we present an integration of the full all-atom Amber molecular dynamics force field into Phenix crystallographic refinement, which enables a more complete modeling of biomolecular chemistry. The advantages of the force field include a carefully derived set of torsion angle potentials, an extensive and flexible set of atom types, Lennard-Jones treatment of non-bonded interactions and a full treatment of crystalline electrostatics. The new combined method was tested against conventional geometry restraints for over twenty-two thousand protein structures. Structures refined with the new method show substantially improved model quality. On average, Ramachandran and rotamer scores are somewhat better; clash scores and MolProbity scores are significantly improved; and the modelling of electrostatics leads to structures that exhibit more, and more correct, hydrogen bonds than those refined with traditional geometry restraints. We find in general that model improvements are greatest at lower resolutions, prompting plans to add the Amber target function to real-space refinement for use in electron cryo-microscopy. This work opens the door to the future development of more advanced applications such as Amber-based ensemble refinement, quantum mechanical representation of active sites and improved geometric restraints for simulated annealing. This document contains embedded data - to preserve data integrity, please ensure where possible that the IUCr Word tools (available from http://journals.iucr.org/services/docxtemplate/ ) are installed when editing this document. The full Amber force field has been integrated into Phenix as an alternative refinement target. With a slight loss in speed, it achieves improved stereochemistry, fewer steric clashes and better hydrogen bonds.

59 BASIC BIOLOGICAL SCIENCES↗