Electron-Density Descriptors as Predictors in Quantitative Structure–Activity/Property Relationships and Drug Design

Matta, Chérif F.; Arabi, Alya A.

doi:10.4155/fmc.11.65

Cited by 65 publications

(65 citation statements)

References 134 publications

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“…These properties can be grouped in three broad classes: (1) Atomic properties such as atomic energy, atomic charge, and atomic electric multipoles, are integrated over the (finite) atomic basin (Bader 1990); (2) Integrated interatomic properties such as the delocalization index (Fradera et al 1999) or the interacting-quantum-atoms (IQA) interaction energy component (Blanco et al 2005) obtained from integrals over the basins of pairs of atoms; and (3) Bond properties (Bader 1990) which can be further subdivided into those that are locally determined at the bond critical point (BCP) such as the electron density or the energy density evaluated at the BCP, or integrated along the bond path such as the bond path length, or integrated over the interatomic zero-flux surface such as the integrated electron density over the interatomic surface. Atomic properties have been used extensively to accommodate and predict a large array of experimentally verifiable quantities including for example heats of formation (Wiberg et al 1987), magnetic susceptibility , molecular volumes , polarizability ), Raman intensities , IR intensities (Gough et al 2007;Matta and Boyd 2007;César et al 2005) UV transition probabilities (Bader et al 2000), physicochemical properties of series of biological molecules (Matta and Arabi 2011), and more. These properties include static and response properties, an example of the latter being the polarizability.…”

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confidence: 99%

Special issue: Philosophical aspects and implications of the quantum theory of atoms in molecules (QTAIM)

Matta

2013

Found Chem

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mentioning

confidence: 99%

Special issue: Philosophical aspects and implications of the quantum theory of atoms in molecules (QTAIM)

Matta

2013

Found Chem

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“…The AIMAll/AIMStudio is comprehensive, yielding a complete sets of bond and atomic properties, and also includes an excellent graphical-user interface for the visualization of the results. QTAIM bond and atomic properties are easy to calculate and were shown to provide an excellent basis for quantitative structure-activity relationship-type studies and also rational approaches to drug design ( [36] and the literature cited therein).…”

Section: Editorial | Matta and Massamentioning

confidence: 99%

“…The use of subsystem quantum mechanics such as QTAIM [36] and KEM [25] in drug design is still in its infancy, but given its considerable utility and direct relevance to medicinal chemistry its general application in this field of science is, perhaps, just a matter of time.…”

Section: Editorial | Matta and Massamentioning

confidence: 99%

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Subsystem Quantum Mechanics and In Silico Medicinal and Biological Chemistry

Matta

Massa

2011

Future Med. Chem.

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EditorialIn silico (or computational) biochemistry is a growing subfield of medicinal and biological chemistry. The growth of research in this area has accelerated at a dramatic rate during the past two decades given the phenomenal increase in the speed of computing and the drastic reduction of its costs. These technological advances were paralleled by no less spectacular conceptual advances in theoretical chemistry, bringing highquality electronic structure calculations, the full interpretative power of quantum mechanics, and computational speed together at the desktop of the practicing chemist. The pioneering early work of the Pullmans in the sixties has now come a very long way in modeling, interpreting and predicting the chemistry of life [1,2]. This relatively new Journal has already devoted a series of three special issues this year to computational medicinal chemistry, an initiative that underscores the importance of this emerging field in medicinal chemistry [3][4][5].The developments alluded to above may be classified into two broad categories: theories and methods that yield results of comparable quality to post-Hartree-Fock electronic structure methods, such as configuration interaction methods, but at a small fraction of the computational cost; and quantum mechanical theoretical advances that provide insight into the results of the calculations.A prime example of a new theory that often yields configuration interaction quality results at a much lower cost is density functional theory (DFT) [6,7], developed by Nobel Laureate Walter Kohn in the 1960s and that is now a widely used mature field.The advances in electronic structure methods were both theoretical (e.g., the development of new hybrid functionals, a noted example being the B3LYP [8,9] hybrid DFT functional) and also algorithmic by incorporating them into standard quantum mechanical codes such as GAMESS and Gaussian. DFT brought the cost of highquality calculations that incorporate Coulombic electron correlation to the fingertips of the average chemist, when the use of post-Hartree-Fock methods is impractical. But these advances were not all. Given that medicinal and biological chemists are typically interested in very large molecules, several innovations attacked the problem from a different angle: that of slowing down the scaling of the calculations with size.A number of methods were developed that focus on a region of the molecule such as an active site to study, for example, the catalysis of a biochemical reaction at this site or to compute and compare the binding energies of several substrates. These methods generally partition the system in layers surrounding the active site, with subsequent layers (subsystems) treated at more economical computational levels, with the active site being treated at the most accurate level and the layer most distant from it at the lowest level. A widely used example of this multilayered approach is the quantum mechanics/molecular mechanics approach [10][11][12][13][14].In other instances, the entire molecule...

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“…Это позволит изучать активность не только связывания блокаторов [48], но и модуляторов каналов [49], обладающих небинарной логикой действия, нечеткость которой задается количеством вероятных устойчивых состояний каналов в их присутствии, определяемым с использованием теории функционала плотности, следовательно, дескрипторов электронной плотности, выполняющих роль предиктора свойств многих фармакофоров каналомных препаратов [50].…”

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Correlational Patch-Clamp Spectrometry of the Ion Channels

Градов¹

2017

Preprint

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Membrane ion channels operate in accordance with the main principles of coordination chemistry. Coordination number is known to determine the ion selectivity of the sodium and potassium channels. there are known both ligand-dependent and ligand-controlled ion channels operating within the supramolecular coordination fixation principles. The channelforming ionophores form the structures which bind cations via coordination bonds leading to the conformational changes with the adjustment of the whole supramolecular architecture providing the ion channel selectivity. Such kind of non-covalent systems underlie the electrogenic membrane functions and the potential-controlled transmembrane ion transfer systems. They can be studied by means of the path-clamp method (i.e. the local membrane potential fixation), such as the «anion clamp», applied together with the analysis of the metal ion coordination geometry with the ion channels. However, such methods are not capable to register the ion channel conformational state in situ -during the ion coordination -with the molecular resolution of the ion channel structure. In this regard there is a need to develop dynamical methods capable of the simultaneous registration of the conformational and metallomic / elementomic coordination parameters and the electrophysiological response to the ion coordination. We propose to develop for this purpose a special kind of spectroscopic systems providing registration of the electrophysiological parameters and the single ion channel response by means of the local potential fixation techniques (patch-clamp / voltageclamp) with the advanced spectral processing and the subsequent data mining, with the simultaneous spectral detection of the ion channel state as a coordination and conformationally labile supramolecular structure, with the final data processing results presented not as the single spectra, but as the spectral correlogram.

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Electron-Density Descriptors as Predictors in Quantitative Structure–Activity/Property Relationships and Drug Design

Cited by 65 publications

References 134 publications

Special issue: Philosophical aspects and implications of the quantum theory of atoms in molecules (QTAIM)

Special issue: Philosophical aspects and implications of the quantum theory of atoms in molecules (QTAIM)

Subsystem Quantum Mechanics and In Silico Medicinal and Biological Chemistry

Correlational Patch-Clamp Spectrometry of the Ion Channels

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