Stereochemistry and Validation of Macromolecular Structures

Wlodawer, Alexander

doi:10.1007/978-1-4939-7000-1_24

Cited by 49 publications

(43 citation statements)

References 54 publications

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“…The instability index and theoretical PI also suggested that the vaccine is stable and basic in nature and the estimated half-life suggested that the recognized peptide does not possess a short half-life and would remain viable for a span adequate to generate a potential immune response. Vaccine model refinement and validation indicated that quality of the predicted model was good as more than 90% residues were in the favored region [55]. The B-cell continuous epitopes predicted over the surface of the vaccine suggested that the vaccine is capable to get recognized by B-cells indicating its effectiveness.…”

Section: Discussionmentioning

confidence: 99%

Designing a multi-epitope peptide-based vaccine against SARS-CoV-2

Singh

Thakur

Sharma

et al. 2020

Preprint

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14COVID-19 pandemic has resulted so far 14,395,16 confirmed cases with 85,711 deaths from the 15 212 countries, or territories. Due to multifacet issues and challenges in implementation of the 16 safety & preventive measures, inconsistent coordination between societies-governments and 17 most importanly lack of specific vaccine to SARS-CoV-2, the spread of Wuhan originated virus 18 is still uprising after taking a heavy toll on human life. In the present study, we mapped several 19 immunogenic epitopes (B-cell, T-cell, and IFN-gamma) over the entire structural proteins of 20 SARS-CoV-2 and by applying various computational and immunoinformatics approaches, we 21 designed a multi-epitope peptide based vaccine that predicted high immunogenic response in the 22 largest proportion of world's human population. To ensure high expression of the recombinant 23 vaccine in E. coli, codon optimization and in-silico cloning were also carried out. The designed 24 vaccine with high molecular affinity to TLR3 and TLR4, was found capable to initiate effective 25 innate and adaptive immune response. The immune simulation also suggested uprising high 26 levels of both B-cell and T-cell mediated immunity which on subsequent exposure cleared 27 antigen from the system. The proposed vaccine found promising by yielding desired results and 28 hence, should be tested by practical experimentations for its functioning and efficacy to 29 neutralize SARS-CoV-2.30 was not certified by peer review)

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Section: Discussionmentioning

confidence: 99%

Designing a multi-epitope peptide-based vaccine against SARS-CoV-2

Singh

Thakur

Sharma

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Fitting atoms in an electron density map and building an accurate and reliable model of the investigated molecule is a complex and multi-parameter task. Although many tools are available for evaluating the reliability of a protein structure, based on the analysis of quality of the stereochemistry of the model as well as on the agreement with experimental data [19], quality of the refinement is often summarized with two numbers, the so-called R and R free factors. These values correspond to the ability of the model to explain experimental data, for data that were used for building and refining the model, in the case of the R-factor, or for a subset of the data that was not used to derive the model, in the case of the R free [20].…”

Section: Theoretical Aspectsmentioning

confidence: 99%

Protein X-ray Crystallography and Drug Discovery

2020

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With the advent of structural biology in the drug discovery process, medicinal chemists gained the opportunity to use detailed structural information in order to progress screening hits into leads or drug candidates. X-ray crystallography has proven to be an invaluable tool in this respect, as it is able to provide exquisitely comprehensive structural information about the interaction of a ligand with a pharmacological target. As fragment-based drug discovery emerged in the recent years, X-ray crystallography has also become a powerful screening technology, able to provide structural information on complexes involving low-molecular weight compounds, despite weak binding affinities. Given the low numbers of compounds needed in a fragment library, compared to the hundreds of thousand usually present in drug-like compound libraries, it now becomes feasible to screen a whole fragment library using X-ray crystallography, providing a wealth of structural details that will fuel the fragment to drug process. Here, we review theoretical and practical aspects as well as the pros and cons of using X-ray crystallography in the drug discovery process.

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“… e R free is typically ∼4–7% higher than R work . The extremely small R free − R wor k difference might indicate a compromised test data set ( Wlodawer et al, 2008 ; Wlodawer, 2017 ). …”

Section: Glutamate Transportersmentioning

confidence: 99%

“…The quality of crystal structures directly depends on the quality of the x-ray diffraction data that were used for their determination. Several articles and reviews describe valuable tools for evaluation of raw experimental data and solved macromolecular structures ( Kleywegt, 2000 ; Wlodawer et al, 2008 ; Chen et al, 2010 ; Gore et al, 2012 ; Adams et al, 2016 ; Wlodawer, 2017 ).…”

Section: Structural Data Quality Indicatorsmentioning

confidence: 99%

“…Altogether, these parameters are used to analyze the structure quality. While analyzing structural statistics of glutamate transporter homologue structures, we observed that the PDB entries 1XFH , 2NWW , 3KBC , 3V8F , 4P3J , 4OYE , and 4OYF show a very small difference between R work and R free factors, which might indicate that the data that were set aside for R free calculation were used at some stage of refinement ( Wlodawer et al, 2008 ; Wlodawer, 2017 ), and thus could indicate possible overfitting.…”

Section: Structural Data Quality Indicatorsmentioning

confidence: 99%

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