A computational study of structural differences of binding of NADP+ and G6P substrates to G6PD Mediterraneanc.563T, G6PD A−c.202A/c.376G, G6PD Cairoc.404C and G6PD Gazac.536A mutations

2021 ◽  
Vol 89 ◽  
pp. 102572
Author(s):  
Mahmoud Sirdah ◽  
N. Scott Reading ◽  
Hariprasad Vankayalapati ◽  
Josef T. Prchal
Keyword(s):  
Computational Study ◽  
Structural Differences

scholarly journals Structural Insights on the SARS-CoV-2 Variants of Concern Spike Glycoprotein: A Computational Study With Possible Clinical Implications

2021 ◽  
Vol 12 ◽  
Author(s):  
Marni E. Cueno ◽  
Kenichi Imai
Keyword(s):  
Computational Study ◽  
Structural Similarity ◽  
Cross Reactivity ◽  
Spike Protein ◽  
Structural Comparison ◽  
Model Quality ◽  
Contact Mapping ◽  
Phylogenetic Cluster ◽  
Conformational Epitopes ◽  
Structural Differences

Coronavirus disease 2019 (COVID-19) pandemic has been attributed to SARS-CoV-2 (SARS2) and, consequently, SARS2 has evolved into multiple SARS2 variants driving subsequent waves of infections. In particular, variants of concern (VOC) were identified to have both increased transmissibility and virulence ascribable to mutational changes occurring within the spike protein resulting to modifications in the protein structural orientation which in-turn may affect viral pathogenesis. However, this was never fully elucidated. Here, we generated spike models of endemic HCoVs (HCoV 229E, HCoV OC43, HCoV NL63, HCoV HKU1, SARS CoV, MERS CoV), original SARS2, and VOC (alpha, beta, gamma, delta). Model quality check, structural superimposition, and structural comparison based on RMSD values, TM scores, and contact mapping were all performed. We found that: 1) structural comparison between the original SARS2 and VOC whole spike protein model have minor structural differences (TM > 0.98); 2) the whole VOC spike models putatively have higher structural similarity (TM > 0.70) to spike models from endemic HCoVs coming from the same phylogenetic cluster; 3) original SARS2 S1-CTD and S1-NTD models are structurally comparable to VOC S1-CTD (TM = 1.0) and S1-NTD (TM > 0.96); and 4) endemic HCoV S1-CTD and S1-NTD models are structurally comparable to VOC S1-CTD (TM > 0.70) and S1-NTD (TM > 0.70) models belonging to the same phylogenetic cluster. Overall, we propose that structural similarities (possibly ascribable to similar conformational epitopes) may help determine immune cross-reactivity, whereas, structural differences (possibly associated with varying conformational epitopes) may lead to viral infection (either reinfection or breakthrough infection).

scholarly journals Effect of arsenate substitution on phosphate repository of cell: a computational study

2018 ◽  
Vol 5 (11) ◽  
pp. 181565
Author(s):  
Amit Singh ◽  
Kousik Giri
Keyword(s):  
Molecular Mechanics ◽  
Density Functional ◽  
Computational Study ◽  
Basis Set ◽  
Phosphate Esters ◽  
Amber Force Field ◽  
Structural Differences ◽  
Phosphate Species ◽  
Structural Analogy ◽  
The Stability

The structural analogy with phosphate derives arsenate into various metabolic processes associated with phosphate inside the organisms. But it is difficult to evaluate the effect of arsenate substitution on the stability of individual biological phosphate species, which span from a simpler monoester form like pyrophosphate to a more complex phosphodiester variant like DNA. In this study, we have classified the physiological phosphate esters into three different classes on the basis of their structural differences. This classification has helped us to present a concise theoretical study on the kinetic stability of phosphate analogue species of arsenate against hydrolysis. All the calculations have been carried out using QM/MM methods of our Own N-layer Integrated molecular Orbital molecular Mechanics (ONIOM). For quantum mechanical region, we have used M06-2X density functional with 6-31+G(2d,2p) basis set and for molecular mechanics we have used the AMBER force field. The calculated rate constants for hydrolysis show that none of the phosphate analogue species of arsenate has a reasonable stability against hydrolysis.

scholarly journals Structural Characterization of the CD44 Stem Region for Standard and Cancer-Associated Isoforms

2020 ◽  
Vol 21 (1) ◽  
pp. 336
Author(s):  
Kun-Lin Chen ◽  
Deng Li ◽  
Ting-Xuan Lu ◽  
Shu-Wei Chang
Keyword(s):  
Hydrophobic Interactions ◽  
Prognostic Biomarker ◽  
Structural Information ◽  
Computational Study ◽  
Experimental Studies ◽  
Hydrogen Bonding Interactions ◽  
Structural Differences ◽  
Β Sheets ◽  
Β Sheet

CD44 is widely expressed in most vertebrate cells, whereas the expression of CD44v6 is restricted to only a few tissues and has been considered to be associated with tumor progression and metastasis. Thus, CD44v6 has been recognized as a promising prognostic biomarker and therapeutic target for various cancers for more than a decade. However, despite many experimental studies, the structural dynamics and differences between CD44s and CD44v6, particularly in their stem region, still remain elusive. Here, a computational study was conducted to address these problems. We found that the stem of CD44s adopted predominantly two conformations, one featuring antiparallel β-sheets and the other featuring parallel β-sheets, whereas the stem of CD44v6 adopted mainly one conformation with relatively highly suppressed β-sheet contents. Moreover, Phe215 was found to be essential in the β-sheets of both CD44s and CD44v6. We finally found intramolecular Phe215–Trp224 hydrogen-bonding interactions and hydrophobic interactions with Phe215 that cooperatively drove conformational differences upon the addition of the v6 region to CD44. Our study elucidated the structural differences between the stem regions of CD44s and CD44v6 and thus can offer useful structural information for drug design to specifically target CD44v6 in promising clinical applications.

High Resolution Observations of Ion-Milling Induced Transformation in Synthetic Hollandses

1981 ◽  
Vol 39 ◽  
pp. 114-115 ◽  
Author(s):  
T. J. Headley
Keyword(s):  
High Resolution ◽  
Radioactive Waste Disposal ◽  
Ion Milling ◽  
Minor Elements ◽  
Waste Forms ◽  
Carbon Substrates ◽  
Structural Differences ◽  
Oxide Phases ◽  
Argon Ions ◽  
High Resolution Microscopy

Oxide phases having the hollandite structure have been identified in multiphase ceramic waste forms being developed for radioactive waste disposal. High resolution studies of phases in the waste forms described in Ref. [2] were initiated to examine them for fine scale structural differences compared to natural mineral analogs. Two hollandites were studied: a (Ba,Cs,K)-titan-ate with minor elements in solution that is produced in the waste forms, and a synthesized BaAl2Ti6O16 phase containing ∼ 4.7 wt% Cs2O. Both materials were consolidated by hot pressing at temperatures above 1100°C. Samples for high resolution microscopy were prepared both by ion-milling (7kV argon ions) and by crushing and dispersing the fragments on holey carbon substrates. The high resolution studies were performed in a JEM 200CX/SEG operating at 200kV.

CHEMISTRY OF GONADOTROPHINS IN RELATION TO THEIR ANTIGENIC PROPERTIES

1969 ◽  
Vol 62 (1_Suppl) ◽  
pp. S13-S30 ◽  
Author(s):  
W. R. Butt
Keyword(s):  
Biological Activity ◽  
Guinea Pigs ◽  
Complement Fixation ◽  
Neuraminic Acid ◽  
Fixation Technique ◽  
Immunological Activity ◽  
Antigenic Properties ◽  
Specific Antisera ◽  
Structural Differences

ABSTRACT Several chemical differences between FSH, LH and HCG have been reported: thus LH and HCG are richer in proline than FSH and FSH and HCG contain more N-acetyl neuraminic acid than LH. Sub-units of LH are formed by treatment with urea, guanidine or acid. HCG also may contain two sub-units. The sub-units from LH are biologically inert but retain their immunological activity: biological activity is restored when the sub-units are incubated together. There is much evidence from chemical and enzymic reactions that antigenic groups are distinct from those parts of the molecule essential for biological activity. N-acetyl neuraminic acid and probably other carbohydrates in FSH and HCG are not involved in immunological activity but are necessary for biological activity. Histidine, methionine and possibly cysteine appear to be essential for biological but not immunological activity of FSH, while tryptophan and possibly tyrosine are not essential for either. A few highly specific antisera to gonadotrophins have been prepared in rabbits and guinea pigs to crude antigens: there is no evidence that purified antigens are more likely to produce specific antisera. Differences in the immunological reactivities of urinary compared with pituitary gonadotrophins have been observed both by radioimmunoassay and by the complement fixation technique. The latter may be particularly useful for detecting structural differences in the hormones.

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