Large-Scale Screening Reveals That Geometric Structure Matters More Than Electronic Structure in the Bioinspired Catalyst Design of Formate Dehydrogenase Mimics

ACS Catalysis ◽  
2021 ◽  
pp. 383-396
Author(s):  
Mingjie Liu ◽  
Azadeh Nazemi ◽  
Michael G. Taylor ◽  
Aditya Nandy ◽  
Chenru Duan ◽  
...  
Keyword(s):  
Electronic Structure ◽  
Geometric Structure ◽  
Large Scale ◽  
Formate Dehydrogenase ◽  
Catalyst Design ◽  
Large Scale Screening

scholarly journals Understanding the Role of Geometric and Electronic Structure in Bioinspired Catalyst Design: the Case of Formate Dehydrogenase

2021 ◽  
Author(s):  
Mingjie Liu ◽  
Azadeh Nazemi ◽  
Michael Taylor ◽  
Aditya Nandy ◽  
Chenru Duan ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Density Functional ◽  
Large Scale ◽  
Formate Dehydrogenase ◽  
Molecular Complexes ◽  
Catalyst Design ◽  
Local Geometry ◽  
Structural Variations ◽  
Screening Study ◽  
The Individual

The design of bioinspired synthetic inorganic molecular complexes is challenging, due to a lack of understanding of enzyme action and the degree to which that action can be translated into mimics. Exemplary of this challenge is the reversible conversion of formate into CO2 by formate dehydrogenase (FDH) enzymes with Mo/W centers in large molybdopterin cofactors. Despite numerous efforts to synthesize Mo/W-containing molecular complexes, none have been demonstrated to reproduce the full reactivity of FDH. Here, we carry out a large-scale, high-throughput screening study on all mononuclear Mo/W complexes currently deposited in Cambridge Structural Database (CSD). Using density functional theory, we systematically investigate the individual effects of metal identity, ligand identity, oxidation state, and coordination number on structural, electronic and catalytic properties. We compare our results on molecular complexes with quantum mechanics/molecular mechanics simulations on a representative FDH enzyme to further elucidate the influence of the enzyme environment. These comparisons reveal that the enzyme environment primarily influences the metal-local geometry, and these metal-local structural variations can improve catalysis. Through a series of computational mutations on molecular complexes, we extend beyond the CSD structures to further identify the limits of varied chalcogen and metal identity. This broad set and comparison reveal relatively little variation of electronic properties of the metal center due to the presence of the enzyme environment or changes in metal-distant ligand chemistry. Instead, these properties are found to be much more sensitive to the identity of the metal and the nature of the bound terminal chalcogen.

Training Aides to Screen Children for Speech and Language Problems

1976 ◽  
Vol 7 (4) ◽  
pp. 236-241 ◽  
Author(s):  
Marisue Pickering ◽  
William R. Dopheide
Keyword(s):  
Rural Areas ◽  
Large Scale ◽  
School Personnel ◽  
School Age Children ◽  
Speech And Language ◽  
Elementary School Age ◽  
Evaluation Procedures ◽  
Language Problems ◽  
Competency Based ◽  
Large Scale Screening

This report deals with an effort to begin the process of effectively identifying children in rural areas with speech and language problems using existing school personnel. A two-day competency-based workshop for the purpose of training aides to conduct a large-scale screening of speech and language problems in elementary-school-age children is described. Training strategies, implementation, and evaluation procedures are discussed.

Recent Progress in Machine Learning-based Prediction of Peptide Activity for Drug Discovery

2019 ◽  
Vol 19 (1) ◽  
pp. 4-16 ◽  
Author(s):  
Qihui Wu ◽  
Hanzhong Ke ◽  
Dongli Li ◽  
Qi Wang ◽  
Jiansong Fang ◽  
...  
Keyword(s):  
Machine Learning ◽  
Drug Discovery ◽  
Large Scale ◽  
Recent Progress ◽  
High Specificity ◽  
Learning Approaches ◽  
Anticancer Peptides ◽  
The Past ◽  
Traditional Approaches ◽  
Large Scale Screening

Over the past decades, peptide as a therapeutic candidate has received increasing attention in drug discovery, especially for antimicrobial peptides (AMPs), anticancer peptides (ACPs) and antiinflammatory peptides (AIPs). It is considered that the peptides can regulate various complex diseases which are previously untouchable. In recent years, the critical problem of antimicrobial resistance drives the pharmaceutical industry to look for new therapeutic agents. Compared to organic small drugs, peptide- based therapy exhibits high specificity and minimal toxicity. Thus, peptides are widely recruited in the design and discovery of new potent drugs. Currently, large-scale screening of peptide activity with traditional approaches is costly, time-consuming and labor-intensive. Hence, in silico methods, mainly machine learning approaches, for their accuracy and effectiveness, have been introduced to predict the peptide activity. In this review, we document the recent progress in machine learning-based prediction of peptides which will be of great benefit to the discovery of potential active AMPs, ACPs and AIPs.

scholarly journals Analytical Validation and Clinical Application of Rapid Serological Tests for SARS-CoV-2 Suitable for Large-Scale Screening

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 869
Author(s):  
Amedeo De Nicolò ◽  
Valeria Avataneo ◽  
Jessica Cusato ◽  
Alice Palermiti ◽  
Jacopo Mula ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Real Time Pcr ◽  
Large Scale ◽  
High Sensitivity ◽  
Analytical Validation ◽  
Pcr Assay ◽  
Serological Tests ◽  
Flow Test ◽  
Lateral Flow Test ◽  
Large Scale Screening

Recently, large-scale screening for COVID-19 has presented a major challenge, limiting timely countermeasures. Therefore, the application of suitable rapid serological tests could provide useful information, however, little evidence regarding their robustness is currently available. In this work, we evaluated and compared the analytical performance of a rapid lateral-flow test (LFA) and a fast semiquantitative fluorescent immunoassay (FIA) for anti-nucleocapsid (anti-NC) antibodies, with the reverse transcriptase real-time PCR assay as the reference. In 222 patients, LFA showed poor sensitivity (55.9%) within two weeks from PCR, while later testing was more reliable (sensitivity of 85.7% and specificity of 93.1%). Moreover, in a subset of 100 patients, FIA showed high sensitivity (89.1%) and specificity (94.1%) after two weeks from PCR. The coupled application for the screening of 183 patients showed satisfactory concordance (K = 0.858). In conclusion, rapid serological tests were largely not useful for early diagnosis, but they showed good performance in later stages of infection. These could be useful for back-tracing and/or to identify potentially immune subjects.

scholarly journals BonMOLière: Small-Sized Libraries of Readily Purchasable Compounds, Optimized to Produce Genuine Hits in Biological Screens across the Protein Space

2021 ◽  
Vol 22 (15) ◽  
pp. 7773
Author(s):  
Neann Mathai ◽  
Conrad Stork ◽  
Johannes Kirchmair
Keyword(s):  
Large Scale ◽  
Computational Approach ◽  
Large Sets ◽  
Compound Libraries ◽  
Wide Range ◽  
Protein Space ◽  
High Chance ◽  
Large Scale Screening ◽  
Early Drug ◽  
Selection Of

Experimental screening of large sets of compounds against macromolecular targets is a key strategy to identify novel bioactivities. However, large-scale screening requires substantial experimental resources and is time-consuming and challenging. Therefore, small to medium-sized compound libraries with a high chance of producing genuine hits on an arbitrary protein of interest would be of great value to fields related to early drug discovery, in particular biochemical and cell research. Here, we present a computational approach that incorporates drug-likeness, predicted bioactivities, biological space coverage, and target novelty, to generate optimized compound libraries with maximized chances of producing genuine hits for a wide range of proteins. The computational approach evaluates drug-likeness with a set of established rules, predicts bioactivities with a validated, similarity-based approach, and optimizes the composition of small sets of compounds towards maximum target coverage and novelty. We found that, in comparison to the random selection of compounds for a library, our approach generates substantially improved compound sets. Quantified as the “fitness” of compound libraries, the calculated improvements ranged from +60% (for a library of 15,000 compounds) to +184% (for a library of 1000 compounds). The best of the optimized compound libraries prepared in this work are available for download as a dataset bundle (“BonMOLière”).

scholarly journals Large-scale screening of natural genetic resource in the hydrocarbon-producing microalga Botrycoccus braunii identified novel fast-growing strains

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Koji Kawamura ◽  
Suzune Nishikawa ◽  
Kotaro Hirano ◽  
Ardianor Ardianor ◽  
Rudy Agung Nugroho ◽  
...  
Keyword(s):  
Large Scale ◽  
Biomass Productivity ◽  
Botryococcus Braunii ◽  
Algal Biofuel ◽  
Fast Growing ◽  
Wild Strains ◽  
Glass Tubes ◽  
The Tropics ◽  
Large Scale Screening ◽  
Hydrocarbon Productivity

AbstractAlgal biofuel research aims to make a renewable, carbon–neutral biofuel by using oil-producing microalgae. The freshwater microalga Botryococcus braunii has received much attention due to its ability to accumulate large amounts of petroleum-like hydrocarbons but suffers from slow growth. We performed a large-scale screening of fast-growing strains with 180 strains isolated from 22 ponds located in a wide geographic range from the tropics to cool-temperate. A fast-growing strain, Showa, which recorded the highest productivities of algal hydrocarbons to date, was used as a benchmark. The initial screening was performed by monitoring optical densities in glass tubes and identified 9 wild strains with faster or equivalent growth rates to Showa. The biomass-based assessments showed that biomass and hydrocarbon productivities of these strains were 12–37% and 11–88% higher than that of Showa, respectively. One strain, OIT-678 established a new record of the fastest growth rate in the race B strains with a doubling time of 1.2 days. The OIT-678 had 36% higher biomass productivity, 34% higher hydrocarbon productivity, and 20% higher biomass density than Showa at the same cultivation conditions, suggesting the potential of the new strain to break the record for the highest productivities of hydrocarbons.

scholarly journals Identification of Six Loci in Which Mutations Partially Restore Peroxisome Biogenesis and/or Alleviate the Metabolic Defect of pex2 Mutants in Podospora

Genetics ◽  
2002 ◽  
Vol 161 (3) ◽  
pp. 1089-1099
Author(s):  
Gwenaël Ruprich-Robert ◽  
Véronique Berteaux-Lecellier ◽  
Denise Zickler ◽  
Arlette Panvier-Adoutte ◽  
Marguerite Picard
Keyword(s):  
Sole Carbon Source ◽  
Large Scale ◽  
Podospora Anserina ◽  
Developmental Defect ◽  
Dominant Allele ◽  
Peroxisome Biogenesis ◽  
Metabolic Defects ◽  
Metabolic Defect ◽  
Mutant Strains ◽  
Large Scale Screening

Abstract Peroxins (PEX) are proteins required for peroxisome biogenesis. Mutations in PEX genes cause lethal diseases in humans, metabolic defects in yeasts, and developmental disfunctions in plants and filamentous fungi. Here we describe the first large-scale screening for suppressors of a pex mutation. In Podospora anserina, pex2 mutants exhibit a metabolic defect [inability to grow on medium containing oleic acid (OA medium) as sole carbon source] and a developmental defect (inability to differentiate asci in homozygous crosses). Sixty-three mutations able to restore growth of pex2 mutants on OA medium have been analyzed. They fall in six loci (suo1 to suo6) and act as dominant, allele-nonspecific suppressors. Most suo mutations have pleiotropic effects in a pex2+ background: formation of unripe ascospores (all loci except suo5 and suo6), impaired growth on OA medium (all loci except suo4 and suo6), or sexual defects (suo4). Using immunofluorescence and GFP staining, we show that peroxisome biogenesis is partially restored along with a low level of ascus differentiation in pex2 mutant strains carrying either the suo5 or the suo6 mutations. The data are discussed with respect to β-oxidation of fatty acids, peroxisome biogenesis, and cell differentiation.

scholarly journals Discovery of naturally occurring inhibitors against SARS-CoV-2 3CLpro from Ginkgo biloba leaves via large-scale screening

Fitoterapia ◽  
2021 ◽  
pp. 104909
Author(s):  
Yuan Xiong ◽  
Guang-Hao Zhu ◽  
Hao-Nan Wang ◽  
Qing Hu ◽  
Li-Li Chen ◽  
...  
Keyword(s):  
Ginkgo Biloba ◽  
Large Scale ◽  
Naturally Occurring ◽  
Large Scale Screening

scholarly journals Validation of COVID-19 serologic tests and large scale screening of asymptomatic healthcare workers

2021 ◽  
Author(s):  
Kristin E. Mullins ◽  
VeRonika Merrill ◽  
Matthew Ward ◽  
Brent King ◽  
Peter Rock ◽  
...  
Keyword(s):  
Healthcare Workers ◽  
Large Scale ◽  
Serologic Tests ◽  
Large Scale Screening

scholarly journals Predicting Shifts in Land Suitability for Maize Cultivation Worldwide Due to Climate Change: A Modeling Approach

Land ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 295
Author(s):  
Yuan Gao ◽  
Anyu Zhang ◽  
Yaojie Yue ◽  
Jing’ai Wang ◽  
Peng Su
Keyword(s):  
Climate Change ◽  
Crop Production ◽  
Large Scale ◽  
Land Suitability ◽  
Large Scale Assessment ◽  
Scale Assessment ◽  
Maize Cultivation ◽  
Large Scale Screening ◽  
Selection Of

Suitable land is an important prerequisite for crop cultivation and, given the prospect of climate change, it is essential to assess such suitability to minimize crop production risks and to ensure food security. Although a variety of methods to assess the suitability are available, a comprehensive, objective, and large-scale screening of environmental variables that influence the results—and therefore their accuracy—of these methods has rarely been explored. An approach to the selection of such variables is proposed and the criteria established for large-scale assessment of land, based on big data, for its suitability to maize (Zea mays L.) cultivation as a case study. The predicted suitability matched the past distribution of maize with an overall accuracy of 79% and a Kappa coefficient of 0.72. The land suitability for maize is likely to decrease markedly at low latitudes and even at mid latitudes. The total area suitable for maize globally and in most major maize-producing countries will decrease, the decrease being particularly steep in those regions optimally suited for maize at present. Compared with earlier research, the method proposed in the present paper is simple yet objective, comprehensive, and reliable for large-scale assessment. The findings of the study highlight the necessity of adopting relevant strategies to cope with the adverse impacts of climate change.

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