Best‐Practice DFT Protocols for Basic Molecular Computational Chemistry**

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(42)

Published: Sept. 14, 2022

Nowadays, many chemical investigations are supported by routine calculations of molecular structures, reaction energies, barrier heights, and spectroscopic properties. The lion's share these quantum-chemical applies density functional theory (DFT) evaluated in atomic-orbital basis sets. This work provides best-practice guidance on the numerous methodological technical aspects DFT three parts: Firstly, we set stage introduce a step-by-step decision tree to choose computational protocol that models experiment as closely possible. Secondly, present recommendation matrix guide choice depending task at hand. A particular focus is achieving an optimal balance between accuracy, robustness, efficiency through multi-level approaches. Finally, discuss selected representative examples illustrate recommended protocols effect choices.

Language: Английский

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GEOM, energy-annotated molecular conformations for property prediction and molecular generation

Scientific Data, Journal Year: 2022, Volume and Issue: 9(1)

Published: April 21, 2022

Abstract Machine learning (ML) outperforms traditional approaches in many molecular design tasks. ML models usually predict properties from a 2D chemical graph or single 3D structure, but neither of these representations accounts for the ensemble conformers that are accessible to molecule. Property prediction could be improved by using conformer ensembles as input, there is no large-scale dataset contains graphs annotated with accurate and experimental data. Here we use advanced sampling semi-empirical density functional theory (DFT) generate 37 million conformations over 450,000 molecules. The Geometric Ensemble Of Molecules (GEOM) 133,000 species QM9, 317,000 data related biophysics, physiology, physical chemistry. Ensembles 1,511 BACE-1 inhibition also labeled high-quality DFT free energies an implicit water solvent, 534 further optimized DFT. GEOM will assist development ensembles, generative sample conformations.

Language: Английский

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CREST—A program for the exploration of low-energy molecular chemical space

The Journal of Chemical Physics, Journal Year: 2024, Volume and Issue: 160(11)

Published: March 21, 2024

Conformer–rotamer sampling tool (CREST) is an open-source program for the efficient and automated exploration of molecular chemical space. Originally developed in Pracht et al. [Phys. Chem. Phys. 22, 7169 (2020)] as driver calculations at extended tight-binding level (xTB), it offers a variety molecular- metadynamics simulations, geometry optimization, structure analysis capabilities. Implemented algorithms include procedures conformational sampling, explicit solvation studies, calculation absolute entropy, identification protonation deprotonation sites. Calculations are set up to run concurrently, providing single-node parallelization. CREST designed require minimal user input comes with implementation GFNn-xTB Hamiltonians GFN-FF force-field. Furthermore, interfaces any quantum chemistry force-field software can easily be created. In this article, we present recent developments code show selection applications most important features program. An novelty refactored backend, which provides significant speed-up small or medium-sized drug molecules allows more sophisticated setups, example, mechanics/molecular mechanics minimum energy crossing point calculations.

Language: Английский

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Best‐Practice DFT Protocols for Basic Molecular Computational Chemistry**

Angewandte Chemie, Journal Year: 2022, Volume and Issue: 134(42)

Published: Sept. 14, 2022

Abstract Nowadays, many chemical investigations are supported by routine calculations of molecular structures, reaction energies, barrier heights, and spectroscopic properties. The lion's share these quantum‐chemical applies density functional theory (DFT) evaluated in atomic‐orbital basis sets. This work provides best‐practice guidance on the numerous methodological technical aspects DFT three parts: Firstly, we set stage introduce a step‐by‐step decision tree to choose computational protocol that models experiment as closely possible. Secondly, present recommendation matrix guide choice depending task at hand. A particular focus is achieving an optimal balance between accuracy, robustness, efficiency through multi‐level approaches. Finally, discuss selected representative examples illustrate recommended protocols effect choices.

Language: Английский

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Automated Molecular Cluster Growing for Explicit Solvation by Efficient Force Field and Tight Binding Methods

Journal of Chemical Theory and Computation, Journal Year: 2022, Volume and Issue: 18(5), P. 3174 - 3189

Published: April 28, 2022

An automated and broadly applicable workflow for the description of solvation effects in an explicit manner is introduced. This method, termed quantum cluster growth (QCG), based on semiempirical GFN2-xTB/GFN-FF methods, enabling efficient geometry optimizations MD simulations. Fast structure generation provided using intermolecular force field xTB-IFF. Additionally, approach uses implicit model electrostatic embedding growing clusters. The novel QCG procedure presents a robust tool subsequent application higher-level (e.g., DFT) methods to study molecular geometries explicitly or average spectroscopic properties over ensembles. Furthermore, computation free energy with supermolecular can be carried out QCG. underlying process physically motivated by computing leading-order solute-solvent interactions first account conformational chemical changes due low-energy barrier processes. space explored NCI-MTD algorithm as implemented CREST program, combination metadynamics GFN2-xTB yields realistic solution reasonable energies various systems without introducing many empirical parameters. Computed IR spectra some solutes show better match experimental data compared well-established models.

Language: Английский

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Carbon Nanodots from an In Silico Perspective

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(16), P. 13709 - 13799

Published: Aug. 10, 2022

Carbon nanodots (CNDs) are the latest and most shining rising stars among photoluminescent (PL) nanomaterials. These carbon-based surface-passivated nanostructures compete with other related PL materials, including traditional semiconductor quantum dots organic dyes, a long list of benefits emerging applications. Advantages CNDs include tunable inherent optical properties high photostability, rich possibilities for surface functionalization doping, dispersibility, low toxicity, viable synthesis (top-down bottom-up) from materials. can be applied to biomedicine imaging sensing, drug-delivery, photodynamic therapy, photocatalysis but also energy harvesting in solar cells as LEDs. More applications reported continuously, making this already research field its own. Understanding requires one go levels electrons, atoms, molecules, at different scales using modern molecular modeling correlate it tightly experiments. This review highlights silico techniques studies, chemistry mesoscale, particular reference carbon nanodots, carbonaceous nanoparticles whose structural photophysical not fully elucidated. The role experimental investigation is presented. Hereby, we hope encourage reader investigate apply virtual obtain further insights needed customize these amazing systems novel prospective

Language: Английский

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Online and desktop graphical user interfaces for xtb programme from atomistica.online platform

Molecular Simulation, Journal Year: 2024, Volume and Issue: 50(7-9), P. 560 - 570

Published: March 19, 2024

In this paper, we introduce our development of both online and desktop graphical user interfaces (GUIs) for the xtb programme to enhance accessibility user-friendliness. The field molecular modelling has been profoundly transformed by advent modern semiempirical calculations, with from Prof. Stefan Grimme's group emerging as an exceptionally powerful tool in domain. operates through a command prompt interface, necessitating certain level technical proficiency its users. need use might be repealing some users, such beginners or users who are not dedicated computational techniques. This was primary motivation develop GUIs programme, considering that experienced modellers would also appreciate user-friendly GUI application helps them automate their tasks. represents significant leap forward, allowing execute calculations directly web browsers. Complementing version, extends functionalities available harnessing more extensive capabilities programme. As all other tools atomistica.online project, freely at project's official website – https://atomistica.online.

Language: Английский

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Convergent Protocols for Computing Protein–Ligand Interaction Energies Using Fragment-Based Quantum Chemistry

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

Published: Jan. 2, 2025

Fragment-based quantum chemistry methods offer a means to sidestep the steep nonlinear scaling of electronic structure calculations so that large molecular systems can be investigated using high-level methods. Here, we use fragmentation compute protein-ligand interaction energies in with several thousand atoms, new software platform for managing fragment-based implements screened many-body expansion. Convergence tests minimal-basis semiempirical method (HF-3c) indicate two-body calculations, single-residue fragments and simple hydrogen caps, are sufficient reproduce obtained conventional supramolecular within 1 kcal/mol at about 1% computational cost. We also demonstrate HF-3c results illustrative trends density functional theory basis sets up augmented quadruple-ζ quality. Strategic deployment facilitates converged biomolecular model alongside high-quality sets, bringing

Language: Английский

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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

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Quick-and-Easy Validation of Protein–Ligand Binding Models Using Fragment-Based Semiempirical Quantum Chemistry

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

Published: Jan. 3, 2025

Electronic structure calculations in enzymes converge very slowly with respect to the size of model region that is described using quantum mechanics (QM), requiring hundreds atoms obtain converged results and exhibiting substantial sensitivity (at least smaller models) which amino acids are included QM region. As such, there considerable interest developing automated procedures construct a based on well-defined criteria. However, testing such burdensome due cost large-scale electronic calculations. Here, we show semiempirical methods can be used as alternatives density functional theory (DFT) assess convergence sequences models generated by various protocols. The these tests reduced even further means many-body expansion. We use this approach examine (with size) protein–ligand binding energies. Fragment-based afford well-converged interaction energies tiny fraction required for DFT Two-body interactions between ligand single-residue acid fragments low-cost way "QM-informed" enzyme size, furnishing an automatable active-site model-building procedure. This provides streamlined, user-friendly constructing binding-site requires neither priori information nor manual adjustments. Extension thermochemical should straightforward.

Language: Английский

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