Quantum mechanical electronic structure calculation reveals orientation dependence of hydrogen bond energy in proteins

Mondal, Abhisek; Datta, Saumen

doi:10.1002/prot.25271

Cited by 6 publications

(5 citation statements)

References 22 publications

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“…Acceptors Donors Level of theory Geometric parameters a Lamas et al 70 1992 71 1996 72 1997 13,68 2004 formamide formamide PBE96/aug-cc-pVDZ f (θ), f (φ) Nanda et al 73 2007 - 20 2008 74 2009 -OH(sp 3 ) CH(sp,sp 2 ) IMPT/6-31G** f (φ) Choi et al 75 2009 N-methylacetamide N-methylacetamide B3LYP/6-311G** f (φ) Choi et al 76 2010 69 2011 78 2016 79 2017 Dataset molecules. The molecules we selected for our dataset are depicted in Supplementary Figs.…”

Section: Supplementary Informationmentioning

confidence: 99%

Charting Hydrogen Bond Anisotropy

Santos-Martins¹,

Forli

2019

Preprint

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Hydrogen bond (HB) is an essential interaction in countless phenomena, and regulates the chemistry of life. HBs are characterized by two main features, strength and directionality, with a high degree of heterogeneity across different chemical groups. These characteristics are dependent on the electronic configuration of the atoms involved in the interaction, which, in turn, is influenced strongly by the molecular environment where they are found. Studies based on the analysis of HB in solid phase, such as X-ray crystallography, suffer from significant biases due to the packing forces. These will tend to better describe strong HBs at the expenses of weak ones, which are either distorted or under-represented. Using quantum mechanics (QM), we calculated interaction energies for about a hundred acceptor and donors, in a rigorously defined set of geometries. We performed about 180,000 independent QM calculations, covering all relevant angular components, and mapping strength and directionality in a context free from external biases, with both single-site and cooperative HBs. We show that by quantifying directionality, there is not correlation with strength, and therefore these two components need to be addressed separately. Results demonstrate that there are very strong HB acceptors (e.g., DMSO) with nearly isotropic interactions, and weak ones (e.g., thioacetone) with a sharp directional profile. Similarly, groups can have comparable directional propensity, but be very distant in the strength spectrum (e.g., thioacetone and pyridine). These findings have implications for biophysics and molecular recognition, providing new insight for chemical biology, protein engineering, and drug design. The results require rethinking the way directionality is described, with implications for the thermodynamics of HB. hydrogen bond | drug design | force field | non-covalent interaction Correspondence: forli@scripps.edu ResultsThe dataset contains 34 donors ( Fig.S1) and 67 acceptors ( Fig.S2, Methods). For the entire dataset, calculations were performed using B3LYP density functional with the cc-pVDZ basis set and the counterpoise correction, while MP2/aug-cc-pVTZ with counterpoise correction was used for smaller subsets of complexes. The validation of these two methods, their differences and their effect on the results has been discussed in Supplementary Methods. Strength.We measured the strength of HBs on the 34 donors ( Fig.S1) and 67 acceptors, performing B3LYP/cc-pVDZ calculations of donor-acceptor dimers interacting in optimal ge-July 5, 2019 | 1-20

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Section: Supplementary Informationmentioning

confidence: 99%

Charting Hydrogen Bond Anisotropy

Santos-Martins¹,

Forli

2019

Preprint

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“…Even after more than one century of studies involving a conceptual evolution [1] and applicability in the most diverse fields and research lines [2], the hydrogen bond keeps on evidence as scientific target and questions about it still are highlighted [3], either on structural [4], electronic [5] or thermodynamic [6] points of view. It is widely known that some others more specific areas, such as the spectroscopy [7], for instance, the hydrogen bond has become a mandatory benchmark [8], and it is in this context that the interaction strength rises as one of the main parameters in intermolecular investigations [9].…”

Section: Introductionmentioning

confidence: 99%

The Quantum Electronic Partitioning as Modernization in the Studies of the Intermolecular Interactions

Oliveira

2022

Orbital: Electron. J. Chem.

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Throughout the years, the evolution in the works involving hydrogen bond based on the direct determination of the interaction energy has become limited in order to characterize the electronic nature and interaction strength of the intermolecular system. Through a quantum mechanical formalism, the electronic partitioning has been considered a modernizing methodology in the studies of intermolecular interactions, unveil it at the light of electrostatic, Exchange, dispersion and induction contributions.

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“…Among them, very few calculated interaction energies at nonequilibrium geometries (the ones that did are summarized in Supplementary Table S1). − These few studies lack chemical diversity, as relevant chemical groups such as halogens and sulfur or phosphate oxyacids have never been characterized. Furthermore, with respect to the geometrical degrees of freedom, most studies performed one-dimensional scans along a given interaction angle, and only a few considered more than one angle (Supplementary Table S1).…”

Section: Introductionmentioning

confidence: 99%

Charting Hydrogen Bond Anisotropy

Santos-Martins

Forli

2020

J. Chem. Theory Comput.

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A hydrogen bond (HB) is an essential interaction in countless phenomena, regulating the chemistry of life. HBs are characterized by two features, strength and directionality, with a high degree of heterogeneity across different chemical groups. These characteristics are dependent on the electronic configuration of the atoms involved in the interaction, which, in turn, is influenced strongly by the local molecular environment. Studies based on the analysis of HB in the solid phase, such as X-ray crystallography, suffer from significant biases due to packing forces. These will tend to better describe strong HBs at the expenses of weak ones, which will be either distorted or under-represented. Using quantum mechanics (QM), we calculated interaction energies for about a hundred acceptors and donors in a rigorously defined set of geometries. We performed 180,000 independent QM calculations, covering all relevant angular components, mapping strength and directionality in a context free from external biases, with both single-site and cooperative HBs. By quantifying directionality, we show that there is no correlation with strength; therefore, these two components need to be addressed separately. Results demonstrate that there are very strong HB acceptors (e.g., dimethyl sulfoxide) with nearly isotropic interactions and weak ones (e.g., thioacetone) with a sharp directional profile. Similarly, groups can have comparable directional propensity but be very distant in the strength spectrum (e.g., thioacetone and pyridine). Results provide a new perspective on the way HB directionality is described, with implications for biophysics and molecular recognition that ultimately can influence chemical biology, protein engineering, and drug design.

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Quantum mechanical electronic structure calculation reveals orientation dependence of hydrogen bond energy in proteins

Cited by 6 publications

References 22 publications

Charting Hydrogen Bond Anisotropy

Charting Hydrogen Bond Anisotropy

The Quantum Electronic Partitioning as Modernization in the Studies of the Intermolecular Interactions

Charting Hydrogen Bond Anisotropy

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