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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Robust and Efficient Implicit Solvation Model for Fast Semiempirical Methods

Journal of Chemical Theory and Computation, Journal Year: 2021, Volume and Issue: 17(7), P. 4250 - 4261

Published: June 29, 2021

We present a robust and efficient method to implicitly account for solvation effects in modern semiempirical quantum mechanics force fields. A computationally yet accurate model based on the analytical linearized Poisson–Boltzmann (ALPB) is parameterized extended tight binding (xTB) density functional (DFTB) methods as well recently proposed GFN-FF general field. The perform over broad range of systems applications, from conformational energies transition-metal complexes large supramolecular association reactions charged species. For hydration free small molecules, GFN1-xTB(ALPB) reaching accuracy sophisticated explicitly solvated approaches, with mean absolute deviation only 1.4 kcal/mol compared experiment. Logarithmic octanol–water partition coefficients (log Kow) are computed about 0.65 using GFN2-xTB(ALPB) experimental values indicating consistent description differential solvent effects. Overall, more than twenty solvents each six tested. They readily available xtb dftb+ programs diverse computational applications.

Language: Английский

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Late-stage diversification of indole skeletons through nitrogen atom insertion

Science, Journal Year: 2022, Volume and Issue: 377(6610), P. 1104 - 1109

Published: Sept. 1, 2022

Compared with peripheral late-stage transformations mainly focusing on carbon-hydrogen functionalizations, reliable strategies to directly edit the core skeleton of pharmaceutical lead compounds still remain scarce despite recent flurry activity in this area. Herein, we report skeletal editing indoles through nitrogen atom insertion, accessing corresponding quinazoline or quinoxaline bioisosteres by trapping an electrophilic nitrene species generated from ammonium carbamate and hypervalent iodine. This reactivity relies strategic use a silyl group as labile protecting that can facilitate subsequent product release. The utility highly functional group-compatible methodology context several commercial drugs is demonstrated.

Language: Английский

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DFT exchange: sharing perspectives on the workhorse of quantum chemistry and materials science

Physical Chemistry Chemical Physics, Journal Year: 2022, Volume and Issue: 24(47), P. 28700 - 28781

Published: Jan. 1, 2022

In this paper, the history, present status, and future of density-functional theory (DFT) is informally reviewed discussed by 70 workers in field, including molecular scientists, materials method developers practitioners.

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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Calculation of absolute molecular entropies and heat capacities made simple

Chemical Science, Journal Year: 2021, Volume and Issue: 12(19), P. 6551 - 6568

Published: Jan. 1, 2021

We propose a fully-automated composite scheme for the accurate and numerically stable calculation of molecular entropies by efficiently combining density-functional theory (DFT), semi-empirical methods (SQM), force-field (FF) approximations. The is systematically expandable can be integrated seamlessly with continuum-solvation models. Anharmonic effects are included through modified rigid-rotor-harmonic-oscillator (msRRHO) approximation Gibbs-Shannon formula extensive conformer ensembles (CEs), which generated metadynamics search algorithm extrapolated to completeness. For first time, variations ro-vibrational entropy over CE consistently accounted-for Boltzmann-population average. Extensive tests protocol two standard DFT approaches B97-3c B3LYP-D3 reveal an unprecedented accuracy mean deviations <1 cal mol-1 K-1 (about <1-2%) total gas phase medium-sized molecules. Even hardship case extremely flexible linear alkanes (C14H30-C16H34), errors only about 3 K-1. Comprehensive indicate relatively strong variation conformational on underlying level typical drug molecules, inferring complex potential energy surfaces as main source error. Furthermore, we show some application examples free differences in chemical reactions.

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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Dispersion corrected r2SCAN based global hybrid functionals: r2SCANh, r2SCAN0, and r2SCAN50

The Journal of Chemical Physics, Journal Year: 2022, Volume and Issue: 156(13)

Published: April 4, 2022

The regularized and restored semilocal meta-generalized gradient approximation (meta-GGA) exchange-correlation functional r2SCAN [Furness et al., J. Phys. Chem. Lett. 11, 8208-8215 (2020)] is used to create three global hybrid functionals with varying admixtures of Hartree-Fock "exact" exchange (HFX). resulting r2SCANh (10% HFX), r2SCAN0 (25% r2SCAN50 (50% HFX) are combined the semi-classical D4 London dispersion correction. new assessed for calculation molecular geometries, main-group, metalorganic thermochemistry at 26 comprehensive benchmark sets. These include extensive GMTKN55 database, ROST61, IONPI19 It shown that a moderate admixture HFX leads relative improvements mean absolute deviations 11% (r2SCANh-D4), 16% (r2SCAN0-D4), 1% (r2SCAN50-D4) compared parental semi-local meta-GGA. For organometallic reaction energies barriers, r2SCAN0-D4 yields an even larger improvement 35%. computation structural parameters (geometry optimization) does not systematically profit from admixture. Overall, best variant performs well both main-group better or on par well-established functionals, such as PW6B95-D4 PBE0-D4. Regarding systems prone self-interaction errors (SIE4x4), shows reasonable performance, reaching quality range-separated ωB97X-V functional. Accordingly, in combination sufficiently converged basis set [def2-QZVP(P)] represents robust reliable choice general use thermochemical properties chemistry.

Language: Английский

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