Quantum Mechanical Assessment of Protein–Ligand Hydrogen Bond Strength Patterns: Insights from Semiempirical Tight-Binding and Local Vibrational Mode Theory

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6311 - 6311

Published: March 27, 2023

Hydrogen bonds (HB)s are the most abundant motifs in biological systems. They play a key role determining protein-ligand binding affinity and selectivity. We designed two pharmaceutically beneficial HB databases, database A including ca. 12,000 complexes with 22,000 HBs their geometries, B 400 2200 HBs, bond strengths determined via our local vibrational mode analysis. identified seven major patterns, which can be utilized as de novo QSAR model to predict for specific complex. Glycine was reported amino acid residue both donor acceptor profiles, N-H⋯O frequent type found A. were preferred linear range, strongest. angles range of 100-110°, typically forming intramolecular five-membered ring structures, showed good hydrophobic properties membrane permeability. Utilizing B, we generalized Badger's relationship more than HBs. In addition, strength occurrence maps between each ligand functional groups open an attractive possibility novel drug-design approach drug selectivity affinity, they also serve important tool hit-to-lead process.

Language: Английский

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Decoding Chemical Bonds: Assessment of the Basis Set Effect on Overlap Electron Density Descriptors and Topological Properties in Comparison to QTAIM

The Journal of Physical Chemistry A, Journal Year: 2023, Volume and Issue: 127(38), P. 7997 - 8014

Published: Sept. 13, 2023

Quantum chemical bonding descriptors based on the total and overlap density can provide valuable information about interactions in different systems. However, these be sensitive to basis set used. To address this, numerical treatments of electron have been proposed reduce dependency. In this work, we introduce properties (OPs) obtained through treatment present topology (TOP) for first time. We compare dependency OP TOP with their quantum theory atoms molecules (QTAIM) counterparts, considering density. Three single (C-C, C-O, C-F) bonds ethane, methanol, fluoromethane two double (C═C C═O) ethene formaldehyde were analyzed. Diatomic Li-X X = F, Cl, Br also Eight parameters, including QTAIM OP/TOP descriptors, are used assess at ωB97X-D level using 28 sets from three classes: Pople, Ahlrichs, Dunning. The study revealed that topological exhibit comparatively lesser dependence compared counterparts. Remarkably, retain significance even reduced Similarly, show less than excess polarization functions increases charge concentration interatomic region influences both descriptors. Def2TZVP, 6-31++G(d,p), 6-311++G(d,p), cc-pVDZ, cc-pVTZ, cc-pVQZ demonstrate variability tested bond classes study, particular emphasis triple-ζ quality Ahlrichs' set. recommend against numerous functions, such as augmented Dunning's quadruple-ζ.

Language: Английский

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A Closer Look at the FeS Heme Bonds in Azotobacter vinelandii Bacterioferritin: QM/MM and Local Mode Analysis

Journal of Computational Chemistry, Journal Year: 2025, Volume and Issue: 46(1)

Published: Jan. 3, 2025

ABSTRACT Using the QM/MM methodology and a local mode analysis, we investigated character strength of FeS bonds heme groups in oxidized reduced forms Bacterioferritin from Azotobacter vinelandii . The was correlated with bond length, an energy density at critical point, charge difference F S atoms. Changing oxidation state ferrous to ferric generally makes weaker, longer, more covalent, polar. We also SFeS bending found that stronger bond, stiffer, which could play key role balance between states related biological activities.

Language: Английский

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A Review of Potentials of Carica Papaya Leaves in Dengue Viral Infection – Insights of Clinical and Preclinical Studies

Drug Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Abstract One of the most widespread arboviral diseases in world, dengue virus disease (DVD) is primarily found tropical and subtropical regions, affecting 129 countries. The main way that (DENV) spreads through bite a female Aedes aegypti mosquito. Symptomatic therapy supportive care are primary methods managing patients with DENV infection as there currently no approved antiviral medication for this condition. Since guidelines from AYUSH Ministry, Government India, recommend 10 ml carica papaya leaf extract (CPLE) twice daily seven days, to treat fever clinically, we plan review potential infection. Using terms like dengue, fever, hemorrhagic shock syndrome, papaya, literature was searched databases Medline/PubMed Central/PubMed, Google Scholar, Science Direct, EBSCO, Scopus, Web Science, EMBASE, Directory open access journals (DOAJ), reference lists find articles relevant clinical, in-vivo, in-vitro, in-silico studies evaluating efficacy management viral This included English-language publications supported use treatment but it excluded were duplicates. Numerous preclinical clinical investigations, such studies, have identified papaya's anti-dengue potential. pleiotropic effects including its anti-thrombocytopenic activity, immunomodulatory effects, larvicidal property against mosquito species, also been confirmed by numerous in-vitro in-vivo studies. These can help elevating their platelet count alleviating other symptoms. To hasten recovery reduce hospital stays, may take addition symptomatic treatment. Additional randomized controlled trials would be necessary confirm safety effectiveness CPLE

Language: Английский

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Phytomedical Properties of Carica papaya for Boosting Human Immunity Against Viral Infections

Viruses, Journal Year: 2025, Volume and Issue: 17(2), P. 271 - 271

Published: Feb. 16, 2025

Carica papaya, a tropical fruit-bearing plant, has attracted significant attention for its diverse phytomedical properties and ability to regulate both innate adaptive immunity, making it promising natural therapeutic agent. C. papaya is rich in bioactive compounds that play multifaceted role immunomodulation. These constituents have demonstrated efficacy not only against the dengue virus but also other viral infections, including COVID-19 (Corona Virus Disease 2019), Human Immunodeficiency (HIV), Zika virus, others. The antiviral effects of are achieved through enhance host mitigate inflammation, reduce oxidative stress, inhibit replication, modulate immune responses. mechanisms highlight potential as candidate therapies, paving way further exploration pharmacological applications promoting eco-friendly, accessible healthcare solutions combating diseases. This review highlights extracts inhibiting replication modulating responses, emphasizing need studies clinical trials validate their medically viruses causing human

Language: Английский

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Amazon Plant‐Derived Compounds Suppressing Dengue NS5 Protein: Insights from Computational Drug Development and Network Pharmacology Approach

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(10)

Published: March 7, 2024

Abstract Dengue, a life‐threatening Flavivirus infection, is rampant across 128 tropical and subtropical regions, annually afflicting millions causing 20,000 deaths due to inadequate treatments. Despite the FDA‐approved Dengvaxia vaccine, its limitations necessitate novel drug development. Notably, enzymatic nature of NS5 protein (PDB ID: 3p97) within DENV, responsible for viral RNA synthesis, makes it prime target. Employing Pharmacoinformatics, Molecular Dynamics Simulations, Quantum Mechanics, network pharmacology, we screened compounds from NuBBE, Brazilian Amazon Plant Database, along with reported dengue compounds. Docking yielded promising scores (−11.1 −2.8) (−11 −3.1) kcal/mol, respectively. From 1310 phytochemicals, top emerged: Ramosin, Pectolinarin, hinokinin, sesamin, boasting −11, −9.7, −9.6, surpassing Acetaminophen's −5.8. Validated post‐docking interactions used 100 ns Simulations quantum mechanics. Pharmacokinetics Toxicity analysis aligned ADME norms, showing no undue toxicity. Network pharmacology unveiled connections between bioactive chemicals disease targets. This investigation uncovers potential these inhibit DENV‐3 protein. In vitro, in vivo, cell line assays are crucial next steps specific anti‐dengue

Language: Английский

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Extraction of uranyl from spent nuclear fuel wastewater via complexation—a local vibrational mode study

Journal of Molecular Modeling, Journal Year: 2024, Volume and Issue: 30(7)

Published: June 18, 2024

Abstract Context The efficient extraction of uranyl from spent nuclear fuel wastewater for subsequent reprocessing and reuse is an essential effort toward minimization long-lived radioactive waste. N-substituted amides Schiff base ligands are propitious candidates, where occurs via complexation with the moiety. In this study, we extensively probed chemical bonding in various complexes, utilizing local vibrational modes theory alongside QTAIM NBO analyses. We focused on (i) assessment equatorial O-U N-U bonding, including question chelation, (ii) how strength axial U $$=$$ = O bonds moiety changes upon complexation. Our results reveal that uranium-ligand interactions correlates their covalent character charge donation N lone pairs into vacant uranium orbitals. also found inverse relationship between ligand uranium-oxygen bond. summary, our study provides valuable data a strategic modulation amide towards maximization extraction. Method Quantum chemistry calculations were performed under PBE0 level theory, paired relativistic NESCau Hamiltonian, currently implemented Cologne2020 (interfaced Gaussian16). Wave functions expanded cc-pwCVTZ-X2C basis set Dunning’s cc-pVTZ remaining atoms. For properties, utilized package LModeA analyses, AIMALL calculations, 7.0 Graphical abstract

Language: Английский

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Extraction of uranyl from spent nuclear fuel wastewater via complexation - a local vibrational mode study

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 19, 2024

The efficient extraction of uranyl from spent nuclear fuel wastewater for subsequent reprocessing and reuse in the cycle is an essential effort towards minimization long-lived radioactive waste. N-substituted amides Schiff base ligands are propitious candidates, where occurs via complexation with moiety. In this study, we utilized local vibra- tional modes theory, paired QTAIM NBO analyses, to explore chemical bonding nitrate, two picolinamide, one base, three diamide complexes. major focus was on (i) assessment equatorial uranyl-ligand O-U N-U bonding, includ- ing question chelation, (ii) how strength axial uranium oxygen U=O bonds moiety change upon complexation. Our results reveal that uranium-ligand interactions correlates their covalent character charge donation O N lone pairs into vacant orbitals. We also found inverse relationship between ligand uranium-oxygen bond. summary, our study provides valuable data a strategic modulation amide maximization extraction. Methods: Quantum chemistry calculations were performed PBE0 level relativistic effects accounted NESCau Hamiltonian, implemented Cologne2020, interfaced Gaussian16. use cc-pwCVTZ-X2C basis set Dunning’s cc-pVTZ remaining atoms. Uranium-ligand analyzed LModeA (local vibrational mode analysis), AIMALL (QTAIM 7.0 f(NBO analysis.

Language: Английский

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Exploring the antiviral inhibitory activity of Niloticin against the NS2B/NS3 protease of Dengue virus (DENV2)

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 277, P. 133791 - 133791

Published: July 9, 2024

Language: Английский

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Protective Mechanisms of Carica papaya Leaf Extract and Its Bioactive Compounds Against Dengue: Insights and Prospects

Immuno, Journal Year: 2024, Volume and Issue: 4(4), P. 629 - 645

Published: Dec. 12, 2024

Dengue fever is currently a major global issue, especially in tropical and subtropical countries. The absence of specific antiviral medications supports alternative dengue treatment strategies. South Asian countries have been using Carica papaya leaves as traditional remedy for many years. possesses several biological features, including anti-inflammatory, antiviral, cancer-fighting, anti-diabetic, antioxidant qualities. Additionally, numerous studies demonstrated that bioactive compounds found leaf extracts, carpaine, dehydrocarpaine I II, chymopapain, papain, significantly influence platelet counts, while phenolic compounds, such chlorogenic acid, kaemferol, protocatechuic quercetin, 5,7-dimethoxycoumarin inhibit viral replication patients, with negligible side effects. may be considered viable pharmacological candidate targets treating dengue. It has shown to prevent infections, reduce oxidative stress, control cytokine storms the immune system, lessen thrombocytopenia, increase body’s protein hemoglobin levels. This literature review highlights pathophysiological mechanism dengue, well action papaya, both which combat this debilitating disease. Despite these findings, additional investigation, clinical studies, necessary confirm effectiveness safety papaya-based treatments. address issues like standardizing figuring out best dosages, assessing any drug interactions.

Language: Английский

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