Publicaciones de Julio Caballero
2024
Valdés-Albuernes, Jorge Luis; Díaz-Pico, Erbio; Alfaro, Sergio; Caballero, Julio
Modeling of noncovalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 considering the protein flexibility by using molecular dynamics and cross-docking Artículo de revista
En: Frontiers in Molecular Biosciences, vol. 11, pp. 1374364, 2024, ISSN: 2296-889X.
@article{valdes-albuernes_modeling_2024,
title = {Modeling of noncovalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 considering the protein flexibility by using molecular dynamics and cross-docking},
author = {Jorge Luis Valdés-Albuernes and Erbio Díaz-Pico and Sergio Alfaro and Julio Caballero},
url = {https://www.frontiersin.org/articles/10.3389/fmolb.2024.1374364/full},
doi = {10.3389/fmolb.2024.1374364},
issn = {2296-889X},
year = {2024},
date = {2024-03-01},
urldate = {2024-12-14},
journal = {Frontiers in Molecular Biosciences},
volume = {11},
pages = {1374364},
abstract = {The papain-like protease (PLpro) found in coronaviruses that can be transmitted from animals to humans is a critical target in respiratory diseases linked to Severe Acute Respiratory Syndrome (SARS-CoV). Researchers have proposed designing PLpro inhibitors. In this study, a set of 89 compounds, including recently reported 2-phenylthiophenes with nanomolar inhibitory potency, were investigated as PLpro noncovalent inhibitors using advanced molecular modeling techniques. To develop the work with these inhibitors, multiple structures of the SARS-CoV-2 PLpro binding site were generated using a molecular sampling method. These structures were then clustered to select a group that represents the flexibility of the site. Subsequently, models of the protein-ligand complexes were created for the set of inhibitors within the chosen conformations. The quality of the complex models was assessed using LigRMSD software to verify similarities in the orientations of the congeneric series and interaction fingerprints to determine the recurrence of chemical interactions. With the multiple models constructed, a protocol was established to choose one per ligand, optimizing the correlation between the calculated docking energy values and the biological activities while incorporating the effect of the binding site’s flexibility. A strong correlation (R
2 = 0.922) was found when employing this flexible docking protocol.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The papain-like protease (PLpro) found in coronaviruses that can be transmitted from animals to humans is a critical target in respiratory diseases linked to Severe Acute Respiratory Syndrome (SARS-CoV). Researchers have proposed designing PLpro inhibitors. In this study, a set of 89 compounds, including recently reported 2-phenylthiophenes with nanomolar inhibitory potency, were investigated as PLpro noncovalent inhibitors using advanced molecular modeling techniques. To develop the work with these inhibitors, multiple structures of the SARS-CoV-2 PLpro binding site were generated using a molecular sampling method. These structures were then clustered to select a group that represents the flexibility of the site. Subsequently, models of the protein-ligand complexes were created for the set of inhibitors within the chosen conformations. The quality of the complex models was assessed using LigRMSD software to verify similarities in the orientations of the congeneric series and interaction fingerprints to determine the recurrence of chemical interactions. With the multiple models constructed, a protocol was established to choose one per ligand, optimizing the correlation between the calculated docking energy values and the biological activities while incorporating the effect of the binding site’s flexibility. A strong correlation (R
2 = 0.922) was found when employing this flexible docking protocol.
2 = 0.922) was found when employing this flexible docking protocol.
Barrales-Martínez, César; Illanes-Solis, Claudio; Durán, Rocío; Caballero, Julio
Exploring the electronic and steric effects on the dimerization of intramolecular frustrated Lewis pairs: a comparison between aminoboranes and aminoalanes Artículo de revista
En: Dalton Transactions, vol. 53, no 16, pp. 7000–7011, 2024, ISSN: 1477-9226, 1477-9234.
@article{barrales-martinez_exploring_2024,
title = {Exploring the electronic and steric effects on the dimerization of intramolecular frustrated Lewis pairs: a comparison between aminoboranes and aminoalanes},
author = {César Barrales-Martínez and Claudio Illanes-Solis and Rocío Durán and Julio Caballero},
url = {https://xlink.rsc.org/?DOI=D3DT04274J},
doi = {10.1039/D3DT04274J},
issn = {1477-9226, 1477-9234},
year = {2024},
date = {2024-01-01},
urldate = {2025-01-02},
journal = {Dalton Transactions},
volume = {53},
number = {16},
pages = {7000–7011},
abstract = {The dimerization of intramolecular aminoborane and aminoalane frustrated Lewis pairs was investigated using density functional theory.
,
The dimerization of intramolecular aminoborane and aminoalane frustrated Lewis pairs was investigated using density functional theory. We systematically varied the substituents to gradually increase their bulkiness, including H, CH
3
,
t
-Bu, Ph, and Mes groups. Starting from the most stable conformer of the monomers, a frustrated Lewis pair or classic Lewis adduct, we studied the dimerization process for all systems, revealing significant variations in the Gibbs free energy. Dimerization was favored in four aminoboranes and six aminoalanes, depending on the specific combinations of substituents. Applying an energy decomposition analysis, we found that the preparation energy of the monomers and the non-orbital interactions between them are the primary contributors to the observed energetic differences, showing a clear linear relationship. Additionally, we analyzed the electronic effects by increasing the acidity of the Lewis acid, observing a shift toward endergonic and exergonic directions in aminoboranes and aminoalanes, respectively. This shift was attributed to the stabilization of a classic Lewis adduct. This study underscores three crucial factors influencing dimer formation: (i) substituent size, (ii) stabilization of the classic Lewis adduct conformation, and (iii) covalent radii of the Lewis centers. Understanding these factors is essential for designing FLPs and preventing unwanted dimerization that could affect their catalytic performance in H
2
activation processes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The dimerization of intramolecular aminoborane and aminoalane frustrated Lewis pairs was investigated using density functional theory.
,
The dimerization of intramolecular aminoborane and aminoalane frustrated Lewis pairs was investigated using density functional theory. We systematically varied the substituents to gradually increase their bulkiness, including H, CH
3
,
t
-Bu, Ph, and Mes groups. Starting from the most stable conformer of the monomers, a frustrated Lewis pair or classic Lewis adduct, we studied the dimerization process for all systems, revealing significant variations in the Gibbs free energy. Dimerization was favored in four aminoboranes and six aminoalanes, depending on the specific combinations of substituents. Applying an energy decomposition analysis, we found that the preparation energy of the monomers and the non-orbital interactions between them are the primary contributors to the observed energetic differences, showing a clear linear relationship. Additionally, we analyzed the electronic effects by increasing the acidity of the Lewis acid, observing a shift toward endergonic and exergonic directions in aminoboranes and aminoalanes, respectively. This shift was attributed to the stabilization of a classic Lewis adduct. This study underscores three crucial factors influencing dimer formation: (i) substituent size, (ii) stabilization of the classic Lewis adduct conformation, and (iii) covalent radii of the Lewis centers. Understanding these factors is essential for designing FLPs and preventing unwanted dimerization that could affect their catalytic performance in H
2
activation processes.
,
The dimerization of intramolecular aminoborane and aminoalane frustrated Lewis pairs was investigated using density functional theory. We systematically varied the substituents to gradually increase their bulkiness, including H, CH
3
,
t
-Bu, Ph, and Mes groups. Starting from the most stable conformer of the monomers, a frustrated Lewis pair or classic Lewis adduct, we studied the dimerization process for all systems, revealing significant variations in the Gibbs free energy. Dimerization was favored in four aminoboranes and six aminoalanes, depending on the specific combinations of substituents. Applying an energy decomposition analysis, we found that the preparation energy of the monomers and the non-orbital interactions between them are the primary contributors to the observed energetic differences, showing a clear linear relationship. Additionally, we analyzed the electronic effects by increasing the acidity of the Lewis acid, observing a shift toward endergonic and exergonic directions in aminoboranes and aminoalanes, respectively. This shift was attributed to the stabilization of a classic Lewis adduct. This study underscores three crucial factors influencing dimer formation: (i) substituent size, (ii) stabilization of the classic Lewis adduct conformation, and (iii) covalent radii of the Lewis centers. Understanding these factors is essential for designing FLPs and preventing unwanted dimerization that could affect their catalytic performance in H
2
activation processes.
