Engineering topics

Kelly, Paul

Publications and source records attributed to Kelly, Paul.

5 records

DOE OSTI2024

The seventh blind test of crystal structure prediction: structure generation methods

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern. The use of CSP in the prediction of likely cocrystal stoichiometry was also explored, demonstrating multiple possible approaches. Crystallographic disorder emerged as an important theme throughout the test as both a challenge for analysis and a major achievement where two groups blindly predicted the existence of disorder for the first time. Additionally, large-scale comparisons of the sets of predicted crystal structures also showed that some methods yield sets that largely contain the same crystal structures.

Chemistry↗

DOE OSTI2024

The seventh blind test of crystal structure prediction: structure ranking methods

A seventh blind test of crystal structure prediction has been organized by the Cambridge Crystallographic Data Centre. The results are presented in two parts, with this second part focusing on methods for ranking crystal structures in order of stability. The exercise involved standardized sets of structures seeded from a range of structure generation methods. Participants from 22 groups applied several periodic DFT-D methods, machine learned potentials, force fields derived from empirical data or quantum chemical calculations, and various combinations of the above. In addition, one non-energy-based scoring function was used. Results showed that periodic DFT-D methods overall agreed with experimental data within expected error margins, while one machine learned model, applying system-specific AIMnet potentials, agreed with experiment in many cases demonstrating promise as an efficient alternative to DFT-based methods. For target XXXII, a consensus was reached across periodic DFT methods, with consistently high predicted energies of experimental forms relative to the global minimum (above 4 kJ mol −1 at both low and ambient temperatures) suggesting a more stable polymorph is likely not yet observed. The calculation of free energies at ambient temperatures offered improvement of predictions only in some cases (for targets XXVII and XXXI). Several avenues for future research have been suggested, highlighting the need for greater efficiency considering the vast amounts of resources utilized in many cases.

Chemistry↗

DOE OSTI2020

Targeting tRNA-synthetase interactions towards novel therapeutic discovery against eukaryotic pathogens

The development of chemotherapies against eukaryotic pathogens is especially challenging because of both the evolutionary conservation of drug targets between host and parasite, and the evolution of strain-dependent drug resistance. There is a strong need for new nontoxic drugs with broad-spectrum activity against trypanosome parasites such as Leishmania and Trypanosoma. A relatively untested approach is to target macromolecular interactions in parasites rather than small molecular interactions, under the hypothesis that the features specifying macromolecular interactions diverge more rapidly through coevolution. We computed tRNA Class-Informative Features in humans and independently in eight distinct clades of trypanosomes, identifying parasite-specific informative features, including base pairs and base mis-pairs, that are broadly conserved over approximately 250 million years of trypanosome evolution. Validating these observations, we demonstrated biochemically that tRNA:aminoacyl-tRNA synthetase (aaRS) interactions are a promising target for anti-trypanosomal drug discovery. From a marine natural products extract library, we identified several fractions with inhibitory activity toward Leishmania major alanyl-tRNA synthetase (AlaRS) but no activity against the human homolog. These marine natural products extracts showed cross-reactivity towards Trypanosoma cruzi AlaRS indicating the broad-spectrum potential of our network predictions. We also identified Leishmania major threonyl-tRNA synthetase (ThrRS) inhibitors from the same library. We discuss why chemotherapies targeting multiple aaRSs should be less prone to the evolution of resistance than monotherapeutic or synergistic combination chemotherapies targeting only one aaRS.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS1988

Automated seed manipulation and planting

Activities for the Fall Semester, 1987 focused on investigating the mechanical/electrical properties of wheat seeds and forming various Seed Planting System (SPS) concepts based on those properties. The Electrical Division of the design group was formed to devise an SPS using electrostatic charge fields for seeding operations. Experiments concerning seed separation using electrical induction (rearranging of the charges within the seed) were conducted with promising results. The seeds, when exposed to the high voltage and low current field produced by a Van de Graff generator, were observed to move back and forth between two electrodes. An SPS concept has been developed based on this phenomena, and will be developed throughout the Spring Semester, 1988. The Mechanical Division centered on SPS concepts involving valves, pumps, and fluids to separate and deliver seeds. An SPS idea utilizing the pressure difference caused by air as it rushes out of holes drilled in the wall of a closed container has been formulated and will be considered for future development. Also, a system of seed separation and delivery employing a combination of centrifugal force, friction, and air flow was considered.

Garcia, Ray↗

NASA NTRS1988

Automated seed manipulation and planting

The Mechanical Division fabricated three seed separators utilizing pressure gradients to move and separate wheat seeds. These separators are called minnow buckets and use air, water, or a combination of both to generate the pressure gradient. Electrostatic fields were employed in the seed separator constructed by the Electrical Division. This separator operates by forcing a temporary electric dipole on the wheat seeds and using charged electrodes to attract and move the seeds. Seed delivery to the hydroponic growth tray is accomplished by the seed cassette. The cassette is compatible with all the seed separators, and it consists of a plastic tube threaded with millipore filter paper. During planting operations, the seeds are placed in an empty cassette. The loaded cassette is then placed in the growth tray and nutrient solution provided. The solution wets the filter paper and capillary action draws the nutrients up to feed the seeds. These seeding systems were tested and showed encouraging results. Seeds were effectively separated and the cassette can support the growth of wheat plants. Problems remaining to be investigated include improving the success of delivering the seeds to the cassette and providing adequate spacing between seeds for the electric separator.

Garcia, Ray↗