Ligand- and structure-based identification of GPER-binding small molecules

Ávila-Avilés, R. D.

doi:10.1080/08927022.2023.2171074

“…The DFT optimized structures of (-)-Epicatechin, and metabolites were used to perform a molecular docking by Autodock Vina software 1.2.0 [26,27]. For molecular docking, a previously simulated and validated GPER structure was used [28]. Docking analysis was performed using a grid box of 22.5 x 22.5 x 22.5 Å 3 considering a 0.375 Å point spicing, the grid box was centered in the center of the Carbon ring of Phe 206, considering previous reported analysis [28][29][30].…”

Section: Rigid and Flexible Molecular Docking Analysesmentioning

confidence: 99%

“…For molecular docking, a previously simulated and validated GPER structure was used [28]. Docking analysis was performed using a grid box of 22.5 x 22.5 x 22.5 Å 3 considering a 0.375 Å point spicing, the grid box was centered in the center of the Carbon ring of Phe 206, considering previous reported analysis [28][29][30]. Docking analysis considered an exhaustiveness of 10, performing 10 different molecular docking analyses with a final exhaustiveness of 100.…”

Section: Rigid and Flexible Molecular Docking Analysesmentioning

confidence: 99%

“…The grid box was centered in the center of the Carbon ring of Phe 206. Also, the flex amino acids considered that GPER structure was adjusted to Leu137, Gln138, Met141, Tyr142, Phe208, Gln215, Glu218, and Val219 following previous reported analysis [28]. The exhaustiveness was adjusted to 10, performing 10 different molecular docking analyses with a final exhaustiveness of 100.…”

Section: Rigid and Flexible Molecular Docking Analysesmentioning

confidence: 99%

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(-)-Epicatechin metabolites as a GPER ligands: a theoretical perspective

Ávila-Avilés,

Bahena-Culhuac,

Hernández-Hernández

2024

Preprint

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Diet habits and nutrition quality significantly impact health and disease. Here is delve into the intricate relationship between diet habits, nutrition quality, and their direct impact on health and homeostasis. Focusing on (-)-Epicatechin, a natural flavanol found in various foods like green tea and cocoa, known for its positive effects on cardiovascular health and diabetes prevention. The investigation encompasses the absorption, metabolism, and distribution of (-)-Epicatechin in the human body, revealing a diverse array of metabolites in the circulatory system. Notably, (-)-Epicatechin demonstrates an ability to activate nitric oxide synthase (eNOS) through the G protein-coupled estrogen receptor (GPER). While the precise role of GPER and its interaction with classical estrogen receptors (ERs) remains under scrutiny, the study employs computational methods, including density functional theory, molecular docking, and molecular dynamics simulations, to assess the physicochemical properties and binding affinities of key (-)-Epicatechin metabolites with GPER. DFT analysis revealed distinct physicochemical properties among metabolites, influencing their reactivity and stability. Rigid and flexible molecular docking demonstrated varying binding affinities, with some metabolites surpassing (-)-Epicatechin. Molecular dynamics simulations highlighted potential binding pose variations, while MMGBSA analysis provided insights into the energetics of GPER-metabolite interactions. The outcomes elucidate distinct interactions, providing insights into potential molecular mechanisms underlying the effects of (-)-Epicatechin across varied biological contexts.

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Exploring New Small Molecule Inhibitors for SARS‐CoV‐2 3CLpro: A Comprehensive Computational Study

Hernández‐Hernández,

Ávila‐Avilés

2024

ChemistrySelect

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The SARS‐CoV‐2 3C‐like protease (3CLpro) has emerged as a key target for drug development owing to its crucial role in viral replication of SARS‐CoV‐2 virus. In this study, we employed a ligand‐based virtual screening strategy to identify potential small molecules capable of binding to SARS‐CoV‐2 3CLpro. Using GC376 as a reference compound, we conducted a comprehensive search in a chemical database and identified 178 candidate molecules (CPLs) with structural similarity to GC376. Molecular docking analyses revealed that several CPLs exhibited superior binding affinities to SARS‐CoV‐2 3CLpro compared to GC376. Notably, CPL‐390, CPL‐374, and CPL‐306 displayed the highest binding energies, indicating their potential as inhibitors of SARS‐CoV‐2 3CLpro. Detailed analysis of noncovalent interactions and molecular mechanics generalized Born surface area (MMGBSA) calculations further supported the binding affinity of CPLs to SARS‐CoV‐2 3CLpro. Key interactions with catalytic residues and steric hindrance within the binding pocket highlighted potential inhibition mechanisms for CPL‐306, CPL‐374, and CPL‐390. Moreover, pharmacokinetic analysis indicated that CPL‐306, CPL‐374, and CPL‐390 possessed favorable absorption, distribution, metabolism, and excretion (ADME) properties, positioning them as promising candidates for further drug development. In contrast, GC376 exhibited less favorable pharmacological characteristics, emphasizing the need for novel compounds with improved profiles.

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(-)-Epicatechin metabolites as a GPER ligands: a theoretical perspective

Ávila-Avilés,

Bahena-Culhuac,

Hernández-Hernández

2024

Mol Divers

0

View full text Add to dashboard Cite

Diet habits and nutrition quality significantly impact health and disease. Here is delve into the intricate relationship between diet habits, nutrition quality, and their direct impact on health and homeostasis. Focusing on (-)-Epicatechin, a natural flavanol found in various foods like green tea and cocoa, known for its positive effects on cardiovascular health and diabetes prevention. The investigation encompasses the absorption, metabolism, and distribution of (-)-Epicatechin in the human body, revealing a diverse array of metabolites in the circulatory system. Notably, (-)-Epicatechin demonstrates an ability to activate nitric oxide synthase (eNOS) through the G protein-coupled estrogen receptor (GPER). While the precise role of GPER and its interaction with classical estrogen receptors (ERs) remains under scrutiny, the study employs computational methods, including density functional theory, molecular docking, and molecular dynamics simulations, to assess the physicochemical properties and binding affinities of key (-)-Epicatechin metabolites with GPER. DFT analysis revealed distinct physicochemical properties among metabolites, influencing their reactivity and stability. Rigid and flexible molecular docking demonstrated varying binding affinities, with some metabolites surpassing (-)-Epicatechin. Molecular dynamics simulations highlighted potential binding pose variations, while MMGBSA analysis provided insights into the energetics of GPER-metabolite interactions. The outcomes elucidate distinct interactions, providing insights into potential molecular mechanisms underlying the effects of (-)-Epicatechin across varied biological contexts.

show abstract

Ligand- and structure-based identification of GPER-binding small molecules

Cited by 4 publications

References 43 publications

(-)-Epicatechin metabolites as a GPER ligands: a theoretical perspective

(-)-Epicatechin metabolites as a GPER ligands: a theoretical perspective

Exploring New Small Molecule Inhibitors for SARS‐CoV‐2 3CLpro: A Comprehensive Computational Study

(-)-Epicatechin metabolites as a GPER ligands: a theoretical perspective

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