Popular Integration Grids Can Result in Large Errors in DFT-Computed Free Energies

Bootsma, Andrea N.; Wheeler, Steven E.

doi:10.26434/chemrxiv.8864204.v2

Cited by 29 publications

(37 citation statements)

References 47 publications

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“…Note that for the largest system with 94 atoms (lopinavir) the frequency calculation took about 7.5 and 0.03 hr, respectively, at the DFT and SQM levels showing the tremendous speed‐up at very little loss of accuracy. Furthermore, the severe sensitivity of DFT‐computed thermostatistical data (vibrational partition function) on the numerical integration grid for low‐frequency modes has been pointed out recently 159 . Eliminating this issue would require the use of very large, computationally costly integration grids in the calculation of the nuclear Hessians with DFT methods.…”

Section: Example Applications and Benchmarkingmentioning

confidence: 99%

Extended tight‐binding quantum chemistry methods

Bannwarth

Caldeweyher

Ehlert

et al. 2020

WIREs Comput Mol Sci

988

964

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This review covers a family of atomistic, mostly quantum chemistry (QC) based semiempirical methods for the fast and reasonably accurate description of large molecules in gas and condensed phase. The theory is derived from a density functional (DFT) perturbation expansion of the electron density in fluctuation terms to various orders similar to the original density functional tight binding model. The term “eXtended” in their name (xTB) emphasizes the parameter availability for almost the entire periodic table of elements (Z ≤ 86) and improvements of the underlying theory regarding, for example, the atomic orbital basis set, the level of multipole approximation and the treatment of the important electrostatic and dispersion interactions. A common feature of most members is their consistent parameterization on accurate gas phase theoretical reference data for geometries, vibrational frequencies and noncovalent interactions, which are the primary properties of interest in typical applications to systems composed of up to a few thousand atoms. Further specialized versions were developed for the description of electronic spectra and corresponding response properties. Besides a provided common theoretical background with some important implementation details in the efficient and free xtb program, various benchmarks for structural and thermochemical properties including (transition‐)metal systems are discussed. The review is completed by recent extensions of the model to the force‐field (FF) level as well as its application to solids under periodic boundary conditions. The general applicability together with the excellent cost‐accuracy ratio and the high robustness make the xTB family of methods very attractive for various fields of computer‐aided chemical research. This article is categorized under: Electronic Structure Theory > Ab Initio Electronic Structure Methods Electronic Structure Theory > Semiempirical Electronic Structure Methods Software > Quantum Chemistry

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Section: Example Applications and Benchmarkingmentioning

confidence: 99%

Extended tight‐binding quantum chemistry methods

Bannwarth

Caldeweyher

Ehlert

et al. 2020

WIREs Comput Mol Sci

988

964

View full text Add to dashboard Cite

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“…using the Gibbs free energy value of -271.9 kcal/mol for the proton in solvent. [50][51][52] The training set and linear regressions used in this work can be found in the Supporting Information (Table S1 and Table S2). The pK a of the terminal Thr1N atom is documented to range from 6 to 9.…”

Section: Resultsmentioning

confidence: 99%

Theoretical Studies of the Acid-Base Equilibria in a Model Active Site of the Human 20S Proteasome

Uranga

Hasecke²,

Proppe³

et al. 2020

Preprint

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The 20S Proteasome is a macromolecule responsible for the chemical step in the ubiquitin-proteasome system of degrading unnecessary and unused proteins of the cell. It plays a central role both in the rapid growth of cancer cells as well as in viral infection cycles. Herein, we present a computational study of the acid-base equilibria in an active site of the human proteasome, an aspect which is often neglected despite the crucial role protons play in the catalysis. As example substrates, we take the inhibition by epoxy and boronic acid containing warheads. We have combined cluster quantum mechanical calculations, replica exchange molecular dynamics and Bayesian optimization of non-bonded potential terms in the inhibitors. In relation to the latter, we propose an easily scalable approach to the reevaluation of non-bonded potentials making use of QM/MM dynamics information. Our results show that coupled acid-base equilibria need to be considered when modeling the inhibition mechanism. The coupling between a neighboring lysine and the reacting threonine is not affected by the presence of the inhibitor.

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“…For this reason, we turned our attention to electronic structure methods in the gas phase and implicit DCM solvent (Figure 3 and Table S3). To compare the binding affinity across a range of quinone/Pd2L4 cages, and considering the computational cost and challenges associated with entropy calculations, [63][64][65] we analyzed relative energy differences (∆∆Ebind) rather than Gibbs free energy differences (∆∆Gbind), i.e without considering entropic or zero-point-energy corrections. 66 It is important to note that while reasonably predictions of absolute binding free energies have been presented for organic host-guest complexes, errors of at least 1-4 kcal mol −1 have been reported for such systems, mostly due to vibrational anharmonicity and solvent effects.…”

Section: Efficient Protocol For Binding Affinity Calculationsmentioning

confidence: 99%

Rationalizing the “Diels-Alderase” Activity of Pd2L4 Self-Assembled Metallocages: Enabling the Efficient Prediction of Catalytic Scaffolds

Young¹,

Martí‐Centelles²,

Wang³

et al. 2019

Preprint

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Self-assembled cages have emerged as novel platforms to explore bio-inspired catalysis. While many different size and shape supramolecular structures are now readily accessible, only a few are proficient catalysts. Here we show that a simple and efficient DFT-based methodology i is sufficient to accurately reproduce experimental binding affinities (MAD = 1.9 kcal mol-1) and identify the catalytic and non-catalytic Diels-Alder proficiencies (>90 % accuracy) of two homologous Pd2L4 metallocages with a variety of substrates. We demonstrate how subtle structural differences in the cage framework affect binding and catalysis, highlighting the critical role of structural dynamics and flexibility on catalytic activity. This flexibility manifests in a smaller transition state distortion energy for the catalytic cage compared to the inactive structure. To facilitate the computational exploration of novel Pd2L4 systems, we introduce an open-source Python module cgbind, which largely automates the screening of novel architectures.

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Popular Integration Grids Can Result in Large Errors in DFT-Computed Free Energies

Cited by 29 publications

References 47 publications

Extended tight‐binding quantum chemistry methods

Extended tight‐binding quantum chemistry methods

Theoretical Studies of the Acid-Base Equilibria in a Model Active Site of the Human 20S Proteasome

Rationalizing the “Diels-Alderase” Activity of Pd2L4 Self-Assembled Metallocages: Enabling the Efficient Prediction of Catalytic Scaffolds

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