Publicaciones de Erbio Díaz-Pico
2026
Valdés-Albuernes, Jorge Luis; Díaz-Pico, Erbio; Velázquez-Libera, José Luis; Caballero, Julio
Computational modeling of ubiquitin specific protease 7 (USP7) complexes with N-benzylpiperidinol derivatives incorporating binding site flexibility Artículo de revista
En: 2026.
@article{Valdés-Albuernes2026,
title = {Computational modeling of ubiquitin specific protease 7 (USP7) complexes with N-benzylpiperidinol derivatives incorporating binding site flexibility},
author = {Jorge Luis Valdés-Albuernes and Erbio Díaz-Pico and José Luis Velázquez-Libera and Julio Caballero },
doi = {10.1016/j.jmgm.2025.109272},
year = {2026},
date = {2026-01-08},
abstract = {Ubiquitin-specific protease 7 (USP7) is a key regulator of protein homeostasis, playing critical roles in various cellular processes, including DNA damage response, immune signaling, and oncogenesis. Targeting USP7 with small-molecule inhibitors has emerged as a promising therapeutic strategy, particularly in the context of cancer and autoimmune diseases. Among the diverse scaffolds explored for USP7 inhibition, N-benzylpiperidinol (NBP) derivatives have shown notable potential due to their structural versatility and bioactivity. Computationally, it is possible to access models of complexes between these inhibitors and USP7 by utilizing the crystallographic structures of USP7 available in the Protein Data Bank. In a classical approach, models of NBPs can be obtained within a rigid USP7 structure. In this work, we report models of complexes between 58 NBPs and variable conformations of USP7 using a flexible docking protocol employing the novel CorrEA method. As part of this protocol, we obtained diverse USP7 structures through molecular dynamics (MD) and selected complex models with inhibitors based on their biological activities. Model quality was validated using LigRMSD and interaction fingerprints (IFP). The flexible treatment of USP7 enabled the capture of binding-site conformational changes. These changes are critical for explaining the activity differences among the studied compounds.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Ubiquitin-specific protease 7 (USP7) is a key regulator of protein homeostasis, playing critical roles in various cellular processes, including DNA damage response, immune signaling, and oncogenesis. Targeting USP7 with small-molecule inhibitors has emerged as a promising therapeutic strategy, particularly in the context of cancer and autoimmune diseases. Among the diverse scaffolds explored for USP7 inhibition, N-benzylpiperidinol (NBP) derivatives have shown notable potential due to their structural versatility and bioactivity. Computationally, it is possible to access models of complexes between these inhibitors and USP7 by utilizing the crystallographic structures of USP7 available in the Protein Data Bank. In a classical approach, models of NBPs can be obtained within a rigid USP7 structure. In this work, we report models of complexes between 58 NBPs and variable conformations of USP7 using a flexible docking protocol employing the novel CorrEA method. As part of this protocol, we obtained diverse USP7 structures through molecular dynamics (MD) and selected complex models with inhibitors based on their biological activities. Model quality was validated using LigRMSD and interaction fingerprints (IFP). The flexible treatment of USP7 enabled the capture of binding-site conformational changes. These changes are critical for explaining the activity differences among the studied compounds.
2025
Valdés-Albuernes, Jorge Luis; Díaz-Pico, Erbio; Alfaro, Sergio; Caballero, Julio
Advanced modeling of salt-inducible kinase (SIK) inhibitors incorporating protein flexibility through molecular dynamics and cross-docking Artículo de revista
En: 2025.
@article{Valdés-Albuernes2025,
title = {Advanced modeling of salt-inducible kinase (SIK) inhibitors incorporating protein flexibility through molecular dynamics and cross-docking},
author = {Jorge Luis Valdés-Albuernes and Erbio Díaz-Pico and Sergio Alfaro and Julio Caballero},
doi = {10.1038/s41598-025-03699-w},
year = {2025},
date = {2025-05-29},
urldate = {2025-05-29},
abstract = {Salt-inducible kinases (SIK1, SIK2, and SIK3) regulate metabolism and immune responses, making them promising targets for inflammatory and autoimmune diseases. Understanding inhibitor selectivity among isoforms is crucial for therapeutic development. In this study, 44 compounds were investigated as SIK inhibitors using molecular modeling. A flexible treatment of the kinases via molecular dynamics (MD) simulations captured binding site conformational changes, followed by molecular docking to generate protein kinase (PK)-ligand complex models. Ligand orientations were validated against crystallographic data using LigRMSD and interaction fingerprints (IFPs). A genetic algorithm was applied to select conformations that maximize correlation between docking energies and biological activities, yielding R² values of 0.821, 0.646, and 0.620 for SIK1, SIK2, and SIK3, respectively. Our results highlight the importance of protein flexibility in achieving accurate correlations between docking energies and experimental pIC50 values, enhancing inhibitor selectivity predictions.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Salt-inducible kinases (SIK1, SIK2, and SIK3) regulate metabolism and immune responses, making them promising targets for inflammatory and autoimmune diseases. Understanding inhibitor selectivity among isoforms is crucial for therapeutic development. In this study, 44 compounds were investigated as SIK inhibitors using molecular modeling. A flexible treatment of the kinases via molecular dynamics (MD) simulations captured binding site conformational changes, followed by molecular docking to generate protein kinase (PK)-ligand complex models. Ligand orientations were validated against crystallographic data using LigRMSD and interaction fingerprints (IFPs). A genetic algorithm was applied to select conformations that maximize correlation between docking energies and biological activities, yielding R² values of 0.821, 0.646, and 0.620 for SIK1, SIK2, and SIK3, respectively. Our results highlight the importance of protein flexibility in achieving accurate correlations between docking energies and experimental pIC50 values, enhancing inhibitor selectivity predictions.
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.
Dreyer, Ingo; Hernández-Rojas, Naomí; Bolua-Hernández, Yasnaya; Tapia-Castillo, Valentina De Los Angeles; Astola-Mariscal, Sadith Z.; Díaz-Pico, Erbio; Mérida-Quesada, Franko; Vergara-Valladares, Fernando; Arrey-Salas, Oscar; Rubio-Meléndez, María E.; Riedelsberger, Janin; Michard, Erwan
Homeostats: The hidden rulers of ion homeostasis in plants Artículo de revista
En: Quantitative Plant Biology, vol. 5, pp. e8, 2024, ISSN: 2632-8828.
@article{dreyer_homeostats_2024,
title = {Homeostats: The hidden rulers of ion homeostasis in plants},
author = {Ingo Dreyer and Naomí Hernández-Rojas and Yasnaya Bolua-Hernández and Valentina De Los Angeles Tapia-Castillo and Sadith Z. Astola-Mariscal and Erbio Díaz-Pico and Franko Mérida-Quesada and Fernando Vergara-Valladares and Oscar Arrey-Salas and María E. Rubio-Meléndez and Janin Riedelsberger and Erwan Michard},
url = {https://www.cambridge.org/core/product/identifier/S2632882824000080/type/journal_article},
doi = {10.1017/qpb.2024.8},
issn = {2632-8828},
year = {2024},
date = {2024-01-01},
urldate = {2024-12-14},
journal = {Quantitative Plant Biology},
volume = {5},
pages = {e8},
abstract = {Abstract
Ion homeostasis is a crucial process in plants that is closely linked to the efficiency of nutrient uptake, stress tolerance and overall plant growth and development. Nevertheless, our understanding of the fundamental processes of ion homeostasis is still incomplete and highly fragmented. Especially at the mechanistic level, we are still in the process of dissecting physiological systems to analyse the different parts in isolation. However, modelling approaches have shown that it is not individual transporters but rather transporter networks (homeostats) that control membrane transport and associated homeostatic processes in plant cells. To facilitate access to such theoretical approaches, the modelling of the potassium homeostat is explained here in detail to serve as a blueprint for other homeostats. The unbiased approach provided strong arguments for the abundant existence of electroneutral H
+
/K
+
antiporters in plants.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Abstract
Ion homeostasis is a crucial process in plants that is closely linked to the efficiency of nutrient uptake, stress tolerance and overall plant growth and development. Nevertheless, our understanding of the fundamental processes of ion homeostasis is still incomplete and highly fragmented. Especially at the mechanistic level, we are still in the process of dissecting physiological systems to analyse the different parts in isolation. However, modelling approaches have shown that it is not individual transporters but rather transporter networks (homeostats) that control membrane transport and associated homeostatic processes in plant cells. To facilitate access to such theoretical approaches, the modelling of the potassium homeostat is explained here in detail to serve as a blueprint for other homeostats. The unbiased approach provided strong arguments for the abundant existence of electroneutral H
+
/K
+
antiporters in plants.
Ion homeostasis is a crucial process in plants that is closely linked to the efficiency of nutrient uptake, stress tolerance and overall plant growth and development. Nevertheless, our understanding of the fundamental processes of ion homeostasis is still incomplete and highly fragmented. Especially at the mechanistic level, we are still in the process of dissecting physiological systems to analyse the different parts in isolation. However, modelling approaches have shown that it is not individual transporters but rather transporter networks (homeostats) that control membrane transport and associated homeostatic processes in plant cells. To facilitate access to such theoretical approaches, the modelling of the potassium homeostat is explained here in detail to serve as a blueprint for other homeostats. The unbiased approach provided strong arguments for the abundant existence of electroneutral H
+
/K
+
antiporters in plants.
0000
Valdés-Albuernes, Jorge Luis; Díaz-Pico, Erbio; Velázquez-Libera, José Luis; Caballero, Julio
Computational modeling of ubiquitin specific protease 7 (USP7) complexes with N-benzylpiperidinol derivatives incorporating binding site flexibility Artículo de revista En preparación
En: En preparación.
@article{nokey,
title = {Computational modeling of ubiquitin specific protease 7 (USP7) complexes with N-benzylpiperidinol derivatives incorporating binding site flexibility},
author = {Jorge Luis Valdés-Albuernes and Erbio Díaz-Pico and José Luis Velázquez-Libera and Julio Caballero},
doi = {10.1016/j.jmgm.2025.109272},
abstract = {Ubiquitin-specific protease 7 (USP7) is a key regulator of protein homeostasis, playing critical roles in various cellular processes, including DNA damage response, immune signaling, and oncogenesis. Targeting USP7 with small-molecule inhibitors has emerged as a promising therapeutic strategy, particularly in the context of cancer and autoimmune diseases. Among the diverse scaffolds explored for USP7 inhibition, N-benzylpiperidinol (NBP) derivatives have shown notable potential due to their structural versatility and bioactivity. Computationally, it is possible to access models of complexes between these inhibitors and USP7 by utilizing the crystallographic structures of USP7 available in the Protein Data Bank. In a classical approach, models of NBPs can be obtained within a rigid USP7 structure. In this work, we report models of complexes between 58 NBPs and variable conformations of USP7 using a flexible docking protocol employing the novel CorrEA method. As part of this protocol, we obtained diverse USP7 structures through molecular dynamics (MD) and selected complex models with inhibitors based on their biological activities. Model quality was validated using LigRMSD and interaction fingerprints (IFP). The flexible treatment of USP7 enabled the capture of binding-site conformational changes. These changes are critical for explaining the activity differences among the studied compounds.
},
keywords = {},
pubstate = {forthcoming},
tppubtype = {article}
}
Ubiquitin-specific protease 7 (USP7) is a key regulator of protein homeostasis, playing critical roles in various cellular processes, including DNA damage response, immune signaling, and oncogenesis. Targeting USP7 with small-molecule inhibitors has emerged as a promising therapeutic strategy, particularly in the context of cancer and autoimmune diseases. Among the diverse scaffolds explored for USP7 inhibition, N-benzylpiperidinol (NBP) derivatives have shown notable potential due to their structural versatility and bioactivity. Computationally, it is possible to access models of complexes between these inhibitors and USP7 by utilizing the crystallographic structures of USP7 available in the Protein Data Bank. In a classical approach, models of NBPs can be obtained within a rigid USP7 structure. In this work, we report models of complexes between 58 NBPs and variable conformations of USP7 using a flexible docking protocol employing the novel CorrEA method. As part of this protocol, we obtained diverse USP7 structures through molecular dynamics (MD) and selected complex models with inhibitors based on their biological activities. Model quality was validated using LigRMSD and interaction fingerprints (IFP). The flexible treatment of USP7 enabled the capture of binding-site conformational changes. These changes are critical for explaining the activity differences among the studied compounds.
