Biology subjects

Medina-Franco, J. L.

Publications and source records attributed to Medina-Franco, J. L..

4 recordsLinked to original sources

bioRxiv2026

SilkRoute: A Descriptor-Driven Framework for Reproducible Multi-Source Biomolecular Data Acquisition

BackgroundBiomolecular dataset construction often requires coordinated retrieval from heterogeneous repositories, identifier mapping, cross-reference enrichment, source-specific parsing, and provenance recording. These operations are frequently implemented through project-specific scripts, making acquisition procedures difficult to inspect, reproduce, or adapt across studies. We present SilkRoute, an open-source Python framework that formalizes biomolecular data acquisition as descriptor-defined, source-aware, and provenance-tracked workflows, providing a reproducible foundation for multi-source biomolecular dataset construction. ResultsSilkRoute uses machine-readable YAML descriptors to specify dataset intent, biomolecular modality, workflow mode, query logic, enrichment resources, execution parameters, and export settings. These descriptors drive a common execution model that coordinates primary retrieval and downstream enrichment while preserving source-specific outputs, interaction evidence when available, the original workflow configuration, metadata, and run summaries. We evaluated this model through three representative acquisition scenarios spanning proteins, compounds, and molecular interactions. In the protein-centered workflow, SilkRoute retrieved 2,444 reviewed antimicrobial protein records from UniProt and generated complementary outputs from AlphaFold DB, InterPro, Pathway Commons, and the Protein Data Bank. In the compound-centered workflow, a ChEMBL IC50 query produced 1,445,939 activity records organized into query-defined potency ranges. In the interaction-centered workflow, 2,253 UniProt protein records were expanded with 902,713 BioGRID interaction records and 5,702 STRING interaction-partner records. Across these scenarios, the framework successfully applied the same descriptor-defined acquisition model to distinct biomolecular entity types, retrieval strategies, enrichment paths, and output structures. ConclusionsSilkRoute extends beyond sequence retrieval by providing a reusable acquisition layer for constructing multi-source biomolecular datasets. By separating primary retrieval from enrichment and preserving source-aware outputs together with workflow descriptors and execution metadata, the framework makes acquisition procedures easier to inspect, reproduce, archive, and adapt. SilkRoute does not replace biological curation, label validation, deduplication, partitioning, or benchmarking, but provides structured and traceable acquisition packages that support these downstream processes.

bioinformatics↗

bioRxiv2025

Daclatasvir, a symmetric drug for an anti-symmetric target

Immunotherapy has become a cornerstone in cancer treatment, with anti-PD-L1 antibodies effectively used across various cancers. Although these therapies have shown success, antibodies face limitations in bioavailability compared to low molecular mass compounds. An alternative strategy is to stabilize PD-L1 homodimers to prevent their immunosuppressive activity. The homodimer interface forms a tunnel-like cavity that can accommodate small molecules. However, no small drugs targeting PD-L1 homodimers have been approved for cancer treatment. Drug repurposing offers a promising approach to bridge this gap. In this study, we sought to identify potential PD-L1 inhibitors among FDA-approved drugs using virtual screening, followed by molecular docking, molecular dynamics simulations, and MM/PBSA binding energy calculations. Our results indicate that daclatasvir, an FDA-approved antiviral for hepatitis C, forms a stable and energetically favorable complex with the PD-L1 homodimer, suggesting it as a promising candidate for further investigation in cancer immunotherapy. Due to its symmetry, daclatasvir simultaneously interacts with both PD-L1 monomers in an equivalent manner, bridging the dimer interface. Its biphenyl core anchors at the center of the tunnel, the imidazole rings position at the entrances, and the pyrrolidine rings remain exposed to the solvent. Our in-depth characterization of the binding mode of daclatasvir clarifies its binding mechanism, and recent experimental findings have also indicated that daclatasvir binds to PD-L1, supporting its potential in this new context.

cancer biology↗

bioRxiv2023

PeruNPDB: The Peruvian Natural Products Database for in silico drug screening

Since the number of drugs based on natural products (NPs) represents a large source of novel pharmacological entities, NPs have acquired significance in drug discovery. Peru is considered a megadiverse country with many endemic species of plants, terrestrial, and marine animals, and microorganisms. NPs databases have a major impact on drug discovery development. For this reason, several countries such as Mexico, Brazil, India, and China have initiatives to assemble and maintain NPs databases that are representative of their diversity and ethnopharmacological usage. We describe the assembly, curation, and full chemoinformatic evaluation of the content and coverage in chemical space, as well as the physicochemical attributes and chemical diversity of the initial version of the Peruvian Natural Products Database (PeruNPDB), which contains 280 compounds. Access to PeruNPDB is available for free (https://perunpdb.com.pe/). The PeruNPDBs collection is intended to be used in a variety of tasks, such as virtual screening campaigns against various disease targets or biological endpoints. This emphasizes the significance of biodiversity protection both directly and indirectly on human health.

bioinformatics↗

bioRxiv2020

DNA Methyltransferase Inhibitors with Novel Chemical Scaffolds

Inhibitors of DNA methyltransferases (DNMTs) are attractive compounds for epigenetic drug discovery. They are also chemical tools to understand the biochemistry of epigenetic processes. Herein, we report five distinct inhibitors of DNMT1 characterized in enzymatic inhibition assays that did not show activity with DNMT3B. It was concluded that the dietary component theaflavin is an inhibitor of DNMT1. Two additional novel inhibitors of DNMT1 are the approved drugs glyburide and panobinostat. The DNMT1 enzymatic inhibitory activity of panobinostat, a known pan inhibitor of histone deacetylases, agrees with experimental reports of its ability to reduce DNMT1 activity in liver cancer cell lines. Molecular docking of the active compounds with DNMT1, and re-scoring with the recently developed Extended Connectivity Interaction Features approach, had an excellent agreement between the experimental IC50 values and docking scores.

systems biology↗