Pattern-free generation and quantum mechanical scoring of ring-chain tautomers

Levine, Daniel S.; Watson, Mark A.; Jacobson, Leif D.; Dickerson, Claire E.; Yu, Haoyu S.; Bochevarov, Arteum D.

doi:10.1007/s10822-020-00334-w

Cited by 3 publications

(3 citation statements)

References 64 publications

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“…As tautomerism involves bond breaking and bond formation, the best way to handle this problem should be quantum mechanics-based approaches by considering the energetics of the individual tautomeric forms. Indeed, methods involving implicit solvent density functional theory calculations have been implemented in the tautomer enumeration and scoring workflow 66 . However, such first-principle calculations are impractical for some of the CADD tasks even with the computation resources nowadays.…”

Section: Resultsmentioning

confidence: 99%

Quantum simulation of preferred tautomeric state prediction

Shee,

Yeh,

Hsiao

et al. 2023

npj Quantum Inf

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Prediction of tautomers plays an essential role in computer-aided drug discovery. However, it remains a challenging task nowadays to accurately predict the canonical tautomeric form of a given drug-like molecule. Lack of extensive tautomer databases, most likely due to the difficulty in experimental studies, hampers the development of effective empirical methods for tautomer predictions. A more accurate estimation of the stable tautomeric form can be achieved by quantum chemistry calculations. Yet, the computational cost required prevents quantum chemistry calculation as a standard tool for tautomer prediction in computer-aided drug discovery. In this paper we propose a hybrid quantum chemistry-quantum computation workflow to efficiently predict the dominant tautomeric form. Specifically, we select active-space molecular orbitals based on quantum chemistry methods. Then we utilize efficient encoding methods to map the Hamiltonian onto quantum devices to reduce the qubit resources and circuit depth. Finally, variational quantum eigensolver (VQE) algorithms are employed for ground state estimation where hardware-efficient ansatz circuits are used. To demonstrate the applicability of our methodology, we perform experiments on two tautomeric systems: acetone and Edaravone, each having 52 and 150 spin-orbitals in the Slater Type Orbital - 3 Gaussian (STO-3G) basis set, respectively. Our numerical results show that their tautomeric state prediction agrees with the Coupled Cluster Singles and Doubles (CCSD) benchmarks. Moreover, the required quantum resources are efficient: in the example of Edaravone, we could achieve chemical accuracy with only eight qubits and 80 two-qubit gates.

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Section: Resultsmentioning

confidence: 99%

Quantum simulation of preferred tautomeric state prediction

Shee,

Yeh,

Hsiao

et al. 2023

npj Quantum Inf

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“…We note that our choice of the number of conformers to generate (200) and optimize by DFT (10) is somewhat arbitrary. These and other settings related to CS have not been carefully optimized in connection with the TS of the oxidation reaction and other conformation-dependent workflows utilizing MacroModel. , However, we believe that the CS parameters selected for the current work, which involves fairly rigid structures, are reasonable and sufficient.…”

Section: Transition State Search Methodologymentioning

confidence: 99%

“…Ortho-aryl-substituted phenyl rings are consistently more reactive than those substituted in the para position, followed by the meta-substituted compounds. Our data set consisted of a significant quantity of data points (52) for phenyl rings, and, therefore, the predicted trend for phenyl rings should be more reliable than the other trends noted in this section.…”

Section: Regioselectivity Trendsmentioning

confidence: 97%

Large Computational Survey of Intrinsic Reactivity of Aromatic Carbon Atoms with Respect to a Model Aldehyde Oxidase

Levine,

Jacobson,

Bochevarov

2023

J. Chem. Theory Comput.

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Quantum chemical package Jaguar: A survey of recent developments and unique features

Cao,

Balduf,

Beachy

et al. 2024

The Journal of Chemical Physics

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This paper is dedicated to the quantum chemical package Jaguar, which is commercial software developed and distributed by Schrödinger, Inc. We discuss Jaguar’s scientific features that are relevant to chemical research as well as describe those aspects of the program that are pertinent to the user interface, the organization of the computer code, and its maintenance and testing. Among the scientific topics that feature prominently in this paper are the quantum chemical methods grounded in the pseudospectral approach. A number of multistep workflows dependent on Jaguar are covered: prediction of protonation equilibria in aqueous solutions (particularly calculations of tautomeric stability and pKa), reactivity predictions based on automated transition state search, assembly of Boltzmann-averaged spectra such as vibrational and electronic circular dichroism, as well as nuclear magnetic resonance. Discussed also are quantum chemical calculations that are oriented toward materials science applications, in particular, prediction of properties of optoelectronic materials and organic semiconductors, and molecular catalyst design. The topic of treatment of conformations inevitably comes up in real world research projects and is considered as part of all the workflows mentioned above. In addition, we examine the role of machine learning methods in quantum chemical calculations performed by Jaguar, from auxiliary functions that return the approximate calculation runtime in a user interface, to prediction of actual molecular properties. The current work is second in a series of reviews of Jaguar, the first having been published more than ten years ago. Thus, this paper serves as a rare milestone on the path that is being traversed by Jaguar’s development in more than thirty years of its existence.

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Pattern-free generation and quantum mechanical scoring of ring-chain tautomers

Cited by 3 publications

References 64 publications

Quantum simulation of preferred tautomeric state prediction

Quantum simulation of preferred tautomeric state prediction

Large Computational Survey of Intrinsic Reactivity of Aromatic Carbon Atoms with Respect to a Model Aldehyde Oxidase

Quantum chemical package Jaguar: A survey of recent developments and unique features

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