A5050526445- Computational Drug Discovery Methods
- Advanced Thermodynamic Systems and Engines
- Machine Learning in Materials Science
- Refrigeration and Air Conditioning Technologies
- Advanced Combustion Engine Technologies
- Protein Structure and Dynamics
- SARS-CoV-2 and COVID-19 Research
- Chemistry and Chemical Engineering
- RNA and protein synthesis mechanisms
- Thermodynamic and Exergetic Analyses of Power and Cooling Systems
- Redox biology and oxidative stress
- Diverse Scientific Research Studies
- Mechanical Engineering and Vibrations Research
- Genomics and Phylogenetic Studies
- Education and Technology Integration
- Mitochondrial Function and Pathology
- Service and Product Innovation
- Parasitic Diseases Research and Treatment
- Plant and animal studies
- Pharmacological Receptor Mechanisms and Effects
- Innovative Microfluidic and Catalytic Techniques Innovation
- Aerodynamics and Fluid Dynamics Research
- Long-Term Effects of COVID-19
- Epilepsy research and treatment
- Outsourcing and Supply Chain Management
Institute of Accelerating Systems and Applications
2023-2024
West Virginia University
2014-2022
Boston VA Research Institute
2020
Harvard University
2020
Yale University
2019
North Carolina State University
2013-2016
Morgantown High School
2015
University of California, Davis
2015
Loyola Marymount University
2013
We report the results of COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. discovered noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, high-throughput structural biology chemistry. generated...
Significant improvements have been made to the OPLS-AA force field for modeling RNA. New torsional potentials were optimized based on density functional theory (DFT) scans at ωB97X-D/6-311++G(d,p) level potential energy surfaces of backbone α and γ dihedral angles. In combination with previously reported sugar puckering glycosidic torsion terms, new was validated through diverse molecular dynamics simulations RNAs in aqueous solution. Results dinucleotides tetranucleotides revealed both...
Shade from neighboring plants limits light for photosynthesis; as a consequence, have variety of strategies to avoid canopy shade and compete with their neighbors light. Collectively the response foliar is called avoidance syndrome (SAS). The SAS includes elongation organs, acceleration flowering time, additional physiological responses, which are seen throughout plant life cycle. However, current mechanistic knowledge mainly limited shade-induced seedlings. Here we use phenotypic profiling...
Abstract Machine learning methods may have the potential to significantly accelerate drug discovery. However, increasing rate of new methodological approaches being published in literature raises fundamental question how models should be benchmarked and validated. We reanalyze data generated by a recently large-scale comparison machine for bioactivity prediction arrive at somewhat different conclusion. show that performance support vector machines is competitive with deep methods....
Abstract We report the results of COVID Moonshot , a fully open-science, crowd sourced, structure-enabled drug discovery campaign targeting SARS-CoV-2 main protease. discovered non-covalent, non-peptidic inhibitor scaffold with lead-like properties that is differentiated from current protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology chemistry. generated detailed map plasticity protease,...
Vaccines and first-generation antiviral therapeutics have provided important protection against COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there remains a need for additional therapeutic options that provide enhanced efficacy potential viral resistance. The SARS-CoV-2 papain-like protease (PL
Article19 October 2020Open Access Transparent process Protein structure, amino acid composition and sequence determine proteome vulnerability to oxidation-induced damage Roger L Chang Corresponding Author [email protected] orcid.org/0000-0003-1630-6584 Department of Systems Biology, Blavatnik Institute at Harvard Medical School, Boston, MA, USA Wyss for Biologically Inspired Engineering, University, Search more papers by this author Julian A Stanley Matthew C Robinson Joel W Sher Zhanwen Li...
Abstract Vaccines and first-generation antiviral therapeutics have provided important protection against coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2). However, there remains a need for additional therapeutic options that provide enhanced efficacy potential viral resistance. The SARS-CoV-2 papain-like protease (PL pro ) is one of two essential cysteine proteases involved in replication. While inhibitors the main (M demonstrated clinical...
Gene conversion is the nonreciprocal exchange of genetic material between homologous chromosomes. Multiple lines evidence from a variety taxa strongly suggest that gene events are biased toward GC-bearing alleles. However, in Drosophila, data have largely been indirect and unclear, with some studies supporting predictions GC-biased model other showing contradictory findings. Here, we test whether Drosophila melanogaster using whole-genome polymorphism divergence data. Our results provide no...
A common challenge in drug design pertains to finding chemical modifications a ligand that increases its affinity the target protein. An underutilized advance is increase structural biology throughput, which has progressed from an artisanal endeavor monthly throughput of hundreds different ligands against protein modern synchrotrons. However, missing piece framework turns high-throughput crystallography data into predictive models for design. Here, we designed simple machine learning...
The effect of applying the exhaust gas recirculation technique on performance a free-piston engine, including resulting emissions, is introduced and assessed in this study. simulation process has been performed over single-cylinder, two-stroke engine that uses homogeneous charge compression ignition. Two main sub-models work implicitly to simulate emissions an iterative procedure using MATLAB® Cantera toolbox. It was found recycling small percentage gases (∼10%) significant reducing like NOx...
For distributed electrical power generation, linear engine-alternator systems have the potential to operate at high efficiency. They avoid frictional losses present in rotating generators and enable use of efficient combustion modes. However, their design control optimization are matters novelty. In this research, a single cylinder, two-stroke, free piston engine model has been built simulated. The describes coupling between motion dynamics chemical kinetics in-cylinder charge mixture...
Abstract A strategy for pandemic preparedness is the development of antivirals against a wide set viral targets with complementary mechanisms action. SARS-CoV-2 nsp3-mac1 macrodomain ADP-ribosylhydrolase activity, which counteracts host immune response. Targeting virus’ immunomodulatory functionality offers differentiated to inhibit compared approved therapeutics, target replication directly. Here we report fragment-based lead generation campaign guided by computational approaches. We...
An Oscillating Linear Engine Alternator (OLEA) has the potential to overcome thermal, mechanical, and combustion inadequacies encountered by conventional slider-crank engines. The linear engines convert reciprocating piston motion into electricity, thereby eliminating needless crankshaft linkages rotational motion. As dead center positions are not explicitly identified unlike engines, engine exhibits different stroke compression ratio every cycle should manage unfavorable events like...
Meiotic recombination is a genetic process that critical for proper chromosome segregation in many organisms. Despite being fundamental organismal fitness, rates of crossing over vary greatly between taxa. Both and environmental factors contribute to phenotypic variation crossover frequency, as do genotype-environment interactions. Here, we test the hypothesis maternal age influences genotypic-specific manner. Using classical techniques, estimated individual Drosophila melanogaster females...
CoPriNet can predict compound prices after being trained on 6M pairs of compounds and collected from the Mcule catalogue.
Purpose The authors found that as more firms participate in open business ecosystems, the borders between an individual firm and its stakeholders – customers, suppliers, workers, partners innovators have become much permeable reconfigurable. This paper aims to address this issue. Design/methodology/approach shows how new models enable maximize benefits of openness while limiting risks. Findings propose three “open firm” based on their research, experience observation: harbor fleet; demand...
The development of molecular descriptors is a central challenge in cheminformatics. Most approaches use algorithms that extract atomic environments or end-to-end machine learning. However, looming question how do these compare with the critical eye trained chemists. CAS fingerprint engages expert chemists to curate chemical motifs, which they deem could influence bioactivity. In this paper, we benchmark against commonly used fingerprints using well-established set 88 targets. We show...