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Dukhovich, F. S.; Gorbatova, E. N.; Kurochkin, V. K.

doi:10.1023/a:1011965322231

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…These mAChR antagonists have the similar molecular weight and size, charge distribution, basicity of the amino group, and the same pharmacophore [2]. In addition, anchoring substituents in the acidic part of molecules have similar partial free energy contributions (ΔΔG) to the mAChR binding free energy: phenyl, thienyl, and cyclohexyl give 2.80, 2.95, and 2.40 kcal/mol, respectively [2,3]. These substances possess high selectivity to muscarinic acetylcholine receptors, not to their specific subtypes [4].…”

Section: Substances Selectionmentioning

confidence: 99%

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Conformational entropy and specific affinity of M-cholinolytics and ligands of µ-opioid and D₂-dopamine receptors

Darkhovskii

Dukhovich

2020

Preprint

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The interest to conformational entropy started from developing new drugs. We show the role of conformational component of the entropy in the complex formation between a substance and a specific neuroreceptor, using M-cholinolytics and ligands of µ-opioid receptors as examples. It is shown that conformational entropy may be used for prediction of the drug affinity to a certain receptor. Examples of directed affinity change under their conformational flexibility modification are given. The specific role of the conformational entropy in the receptor's protection from the irreversible inactivation is identified.

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Section: Substances Selectionmentioning

confidence: 99%

“…Detailed description of the method can be found in [2,3,5]. All investigated substances are synthesized as racemates, so ΔG values of the chiral substances are given in Table 1 for their (R)form, for better comparison with non-chiral substances.…”

Section: δG = Rt Ln Kdmentioning

confidence: 99%

Conformational entropy and specific affinity of M-cholinolytics and ligands of µ-opioid and D₂-dopamine receptors

Darkhovskii

Dukhovich

2020

Preprint

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The Agonist Paradox: Agonists and Antagonists of Acetylcholine Receptors and Opioid Receptors

Dukhovich¹,

Darkhovskii²,

Gorbatova³

et al. 2005

Chemistry & Biodiversity

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In contrast to antagonists, agonists tend to induce considerable conformational changes in their receptors, resulting in opening of ion channels, either directly or via secondary messengers. These conformational transformations require great energy expenses. However, the experimentally determined free energies of complexation between agonists and receptors are often relatively smaller than those for the corresponding antagonists. To rationalize this so-called 'agonist paradox', which has not been clarified in the literature, we have developed an alternative model. Our model may help to discriminate between agonists and antagonists of the acetylcholine (ACh) and mu-opioid receptors. For this purpose, a series of ligands (1-18) have been analyzed both in structural terms and with respect to complexation geometry within the anionic binding sites of these two receptor types.

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Molecular electrostatic potential as a factor of drug–receptor recognition

Dukhovich¹,

Darkhovskii²

2003

J of Molecular Recognition

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When a drug molecule approaches a non-specific acceptor both molecules are in electrostatic fields of equal sign which prevents drug-acceptor complex formation. At the same time, the drug-acceptor system does not achieve the thermodynamic global minimum. Otherwise, when a certain drug interacts with its specific receptor, mutual compensation of their molecular electrostatic potentials takes place. Then separate atoms and groups of the drug molecule can bind to the receptor. We show that the fundamental role of molecular electrostatic potential in the process of drug-receptor recognition consists in fast correction of errors.

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Untitled

Cited by 3 publications

References 6 publications

Conformational entropy and specific affinity of M-cholinolytics and ligands of µ-opioid and D₂-dopamine receptors

Conformational entropy and specific affinity of M-cholinolytics and ligands of µ-opioid and D₂-dopamine receptors

The Agonist Paradox: Agonists and Antagonists of Acetylcholine Receptors and Opioid Receptors

Molecular electrostatic potential as a factor of drug–receptor recognition

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Cited by 3 publications

References 6 publications

Conformational entropy and specific affinity of M-cholinolytics and ligands of µ-opioid and D2-dopamine receptors

Conformational entropy and specific affinity of M-cholinolytics and ligands of µ-opioid and D2-dopamine receptors

The Agonist Paradox: Agonists and Antagonists of Acetylcholine Receptors and Opioid Receptors

Molecular electrostatic potential as a factor of drug–receptor recognition

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Product

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Conformational entropy and specific affinity of M-cholinolytics and ligands of µ-opioid and D₂-dopamine receptors

Conformational entropy and specific affinity of M-cholinolytics and ligands of µ-opioid and D₂-dopamine receptors