End-Point Affinity Estimation of Galectin Ligands by Classical and Semiempirical Quantum Mechanical Potentials

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 4, 2025

The use of quantum mechanical potentials in protein–ligand affinity prediction is becoming increasingly feasible with growing computational power. To move forward, validation such on real-world challenges necessary. this end, we have collated an extensive set over a thousand galectin inhibitors known affinities and docked them into galectin-3. poses were then used to systematically evaluate several modern force fields semiempirical (SQM) methods up the tight-binding level under consistent workflow. Implicit solvation models available tested simulate effects. Overall, best study achieved Pearson correlation 0.7–0.8 between computed experimental affinities. There differences their ability rank ligands across entire ligand as well within subsets structurally similar ligands. A major discrepancy was observed for subset that bind protein via halogen bond, which clearly challenging all methods. inclusion entropic term calculated by rigid-rotor-harmonic-oscillator approximation at SQM slightly worsened experiment but brought closer values. We also found success strongly depended model. Furthermore, provide in-depth analysis individual energy terms effect overall accuracy.

Language: Английский

---

Improving Quantum Chemical Solvation Models by Dynamic Radii Adjustment for Continuum Solvation (DRACO)

The Journal of Physical Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(9), P. 2462 - 2469

Published: Feb. 26, 2024

We present the Dynamic Radii Adjustment for COntinuum solvation (DRACO) approach, which employs precomputed atomic partial charges and coordination numbers of solute atoms to improve cavity. As such, DRACO is compatible with major models, improving their performance significantly robustly at virtually no extra cost, especially charged solutes. Combined purely electrostatic CPCM COSMO reduces mean absolute deviation (MAD) free energy by up 4.5 kcal mol

Language: Английский

---

Distinction and Quantification of Noncovalent Dispersive and Hydrophobic Effects

Molecules, Journal Year: 2024, Volume and Issue: 29(7), P. 1591 - 1591

Published: April 2, 2024

The possibilities of comparing computational results noncovalent interactions with experimental data are discussed, first respect to intramolecular interactions. For these a variety such as heats formation, crystal sublimation heats, comparison energy minimized structures, and spectroscopic available, but until now largely have not found widespread application. Early force field QM/MP2 calculations already shown that the hydrocarbons can be predicted an accuracy ±1%. Intermolecular in solution or gas phase always accompanied by difficult compute entropic contributions, like all associations between molecules. Experimentally observed T∆S values contribute 10% 80% total ∆G, depending on interaction mechanisms within complexes, as, e.g., hydrogen bonding ion pairing. Free energies ∆G derived from equilibrium measurements allow us define binding increments ∆∆G, which additive transferable supramolecular complexes. Data more than 90 porphyrin receptors water indicate small alkanes do bind hydrophobic flat surfaces measuring limit = ±0.5 kJ/mol, 20 functions bearing heteroatoms show dispersive up 8 roughly function their polarizability. Aromatic systems display size-dependent affinities linear number π-electrons.

Language: Английский

---

QupKake: Integrating Machine Learning and Quantum Chemistry for Micro-pK_a Predictions

Journal of Chemical Theory and Computation, Journal Year: 2024, Volume and Issue: 20(15), P. 6946 - 6956

Published: June 4, 2024

Accurate prediction of micro-pKa values is crucial for understanding and modulating the acidity basicity organic molecules, with applications in drug discovery, materials science, environmental chemistry. This work introduces QupKake, a novel method that combines graph neural network models semiempirical quantum mechanical (QM) features to achieve exceptional accuracy generalization prediction. QupKake outperforms state-of-the-art on variety benchmark data sets, root-mean-square errors between 0.5 0.8 pKa units five external test sets. Feature importance analysis reveals role QM both reaction site enumeration models. represents significant advancement prediction, offering powerful tool various chemistry beyond.

Language: Английский

---

Predicting solvation free energies for neutral molecules in any solvent with openCOSMO-RS

Fluid Phase Equilibria, Journal Year: 2024, Volume and Issue: unknown, P. 114250 - 114250

Published: Oct. 1, 2024

Language: Английский

---

Radiation-Induced n-methylacetamide and β-Alanine radicals in aqueous solutions at different pH Levels: EPR spectroscopy and First-Principles calculations

Journal of Molecular Liquids, Journal Year: 2025, Volume and Issue: unknown, P. 127035 - 127035

Published: Jan. 1, 2025

Language: Английский

---

Sonochemical Synthesis of Schiff Base of Substituted Benzoxazolone: A Quantum Chemical, Antibacterial Evaluation and Molecular Docking Study

ChemistrySelect, Journal Year: 2025, Volume and Issue: 10(5)

Published: Feb. 1, 2025

Abstract The derivatives of benzoxazolone (BOA) have attracted a lot interest because their diverse pharmacological potential as therapeutic agents. In this work, we report an environmentally friendly synthetic method based on ultrasonication(US) well conventional to prepare new BOA (M1–M4). Furthermore, the were reacted with p ‐nitro, ‐chloro, and ‐hydroxy anilines get Schiff bases compounds (M5–M16). results demonstrated that, in comparison traditional approaches, ultrasonication had higher reaction kinetics energy efficiency. Additionally, quantum chemical calculations molecular docking studies performed understand mechanisms evaluate antibacterial synthesized compounds. presence electron‐withdrawing group at para position substituted follows trend ─NO 2 > ─Cl ─OH, leading formation energies corresponding products reflected progression reactions mechanistic studies. Further, methyl enhances binding interaction affinity Escherichia coli , however basis scores nitro containing (M5, M8, M11, M14) exhibited stronger interactions protein E. compared chlorine hydroxyl groups. also found consistent vitro results.

Language: Английский

---

Curcumin Electroanalysis at a Disposable Graphite Electrode

Biosensors, Journal Year: 2025, Volume and Issue: 15(3), P. 137 - 137

Published: Feb. 23, 2025

Curcumin (CU, turmeric), a polyphenolic phytochemical that is largely used as food spice, has benefits for human health, which have led to increased interest in its therapeutic applications and analysis from different matrices. The two guaiacol moieties of CU are responsible antioxidant properties allow voltammetric quantification. Cyclic differential pulse voltammetry (DPV) investigations at single-use pencil graphite electrode (PGE) emphasized complex pH-dependent processes, involving an equal number protons electrons. Theoretical calculations predicted folded geometry the β-diketone conformers, interact with PGE surface, exposing electroactive only one aromatic ring. Gibbs energy variations structures involved electro-oxidation theoretical electrochemical potential values were calculated. CU’s DPV cathodic peak intensity recorded HB-type 0.05 mol × L−1 H2SO4 varied linearly range 5.00 10−8–5.00 10−6 CU. method’s detection quantification limits 2.12 10−8 6.42 L−1, respectively. practical applicability developed method, successfully tested by assessment dietary supplements, provided recovery 99.28 ± 2.04%.

Language: Английский

---

Overview on Building Blocks and Applications of Efficient and Robust Extended Tight Binding

The Journal of Physical Chemistry A, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

The extended tight binding (xTB) family of methods opened many new possibilities in the field computational chemistry. Within just 5 years, GFN2-xTB parametrization for all elements up to Z = 86 enabled more than a thousand applications, which were previously not feasible with other electronic structure methods. xTB provide robust and efficient way apply quantum mechanics-based approaches obtaining molecular geometries, computing free energy corrections or describing noncovalent interactions found applicability targets. A crucial contribution success is availability within simulation packages frameworks, supported by open source development its program library packages. We present comprehensive summary applications capabilities different fields Moreover, we consider main software calculations, covering their current ecosystem, novel features, usage scientific community.

Language: Английский

---

ABCG2: A Milestone Charge Model for Accurate Solvation Free Energy Calculation

Journal of Chemical Theory and Computation, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

In this report, we describe the development and validation of ABCG2, a new charge model with milestone free energy accuracy, while allowing instantaneous atomic assignment for arbitrary organic molecules. combination second-generation general AMBER force field (GAFF2), ABCG2 led to root-mean-square error (RMSE) 0.99 kcal/mol on hydration calculation all 642 solutes in FreeSolv database, first time meeting chemical accuracy threshold through physics-based molecular simulation against golden-standard data set. Against Minnesota Solvation Database, solvation 2068 pairs range diverse solvents an RMSE 0.89 kcal/mol. The 1913 points transfer energies from aqueous solution obtained 0.85 kcal/mol, corresponding 0.63 log units logP. benchmark densities neat liquids 1839 molecules heat vaporizations 874 achieved comparable performance default restrained electrostatic potential (RESP) method GAFF2. fluctuations assigned partial charges over different input conformations are demonstrated be much smaller than those RESP statistics 96 real drug results not only but also transferability generality GAFF2/ABCG2 combination.

Language: Английский

---