Ramírez Lab

Pharmacoinformatics & Drug Design

Welcome to the Ramírez Lab

We are a multidisciplinary group focused on the study of biomolecular systems by using theoretical and experimental approaches. We aim to use computational polypharmacology with wet lab analyses to strengthen the drug design and development processes. Our work involves collaboration with medicinal chemists, biochemists, and biologists, and we are part of the Pharmacology Department - Faculty of Biological Sciences at University of Concepción.


Active research areas

  • Pharmacoinformatics & network pharmacology: Multi-target drug design against complex diseases.

  • Drug design by machine learning, artificial intelligence, and data science.

  • Molecular simulations and modeling


  • Latest publication

    Structural Insights into the Substrate Transport Mechanisms in GTR Transporters through Ensemble Docking

    Peña-Varas, C.; Kanstrup, C.; Vergara-Jaque, A.; González-Avendaño, M.; Crocoll, C.; Mirza, O.; Dreyer, I; Nour-Eldin, H.; and Ramírez, D.

    International Journal of Molecular Sciences, 2022, 23(3), 1595; DOI: 10.3390/ijms23031595

    Glucosinolate transporters (GTRs) are part of the nitrate/peptide transporter (NPF) family, members of which also transport specialized secondary metabolites as substrates. Glucosinolates are defense compounds derived from amino acids. We selected 4-methylthiobutyl (4MTB) and indol-3-ylmethyl (I3M) glucosinolates to study how GTR1 from Arabidopsis thaliana transports these substrates in computational simulation approaches. The designed pipeline reported here includes massive docking of 4MTB and I3M in an ensemble of GTR1 conformations (in both inward and outward conformations) extracted from molecular dynamics simulations, followed by clustered and substrate–protein interactions profiling. The identified key residues were mutated, and their role in substrate transport was tested. We were able to identify key residues that integrate a major binding site of these substrates, which is critical for transport activity. In silico approaches employed here represent a breakthrough in the plant transportomics field, as the identification of key residues usually takes a long time if performed from a purely wet-lab experimental perspective. The inclusion of structural bioinformatics in the analyses of plant transporters significantly speeds up the knowledge-gaining process and optimizes valuable time and resources.

    Funding

    Grant Funded by Role Date
    Towards systems pharmacology to design multi-target directed ligands as therapeutic alternatives for Alzheimer’s disease. Chile - Fondecyt Regular No. 1220656 Principal Investigator 2022 – 2025
    Let's talk pharmacology!!! Chile - Universidad de Concepción No. UCO1966 Principal Investigator 2022
    Identificación de moduladores del canal iónico TMC1 como alternativa terapéutica para el tratamiento de la sordera. Chile - ANID No. FOVI210027 Principal Investigator 2022 - 2023
    Development of novel therapeutic alternatives for alcohol-use disorders: a multidisciplinary approach. Chile - ANID No. ACT210012 Deputy Director 2022 - 2025
    Coupling artificial intelligence and neurosciences to potentiate pharmacological actions of tibolone over neuroglobin signaling in traumatic brain injury. Ireland - Science Foundation Ireland Associate Investigator 2021 - 2024
    Reposicionamiento de medicamentos para tratamiento de la pandemia por coronavirus (COVID-19). Chile - ANID No. COVID0199 Principal Investigator 2021 - 2022
    Actualización de los servicios de ANSEP (Astrocyte-neuron simulation environment platform) bajo el estudio integrativo de enfermedades neurodegenerativas. Colombia - Pontificia Universidad Javeriana Associate Investigator 2021 - 2022
    Target- and ligand-based drugs to control SARS-CoV-2 pandemic (CoV2Drugs). Spain - CSIC-COV19-015 Associate Investigator 2020 - 2021
    Multi-Target Drug Design Against Neurodegenerative Diseases. Chile - Conicyt No. REDES190074 Principal Investigator 2020 - 2021
    INSECTR – International Network to Study Secondary Metabolite Transport In Plants. Chile - Conicyt No. REDES1900254 Associate Investigator 2020 - 2021
    Identificación de reacciones controladoras de lipotoxicidad inducida por ácido palmítico en un modelo computacional multiómico astrocitario. Colombia - Colciencias No. 67270 Associate Investigator 2020 - 2022
    Scholarship Programme for Young Professors and Researchers from Latin American Universities. Spain - Coimbra group Principal Investigator 2019
    Structural insights into the substrate specificity and transport mechanisms in the Nitrate/Peptide Transporter (NPF) Family. Chile - Fondecyt Iniciación No. 11180604 Principal Investigator 2018 – 2021
    Análisis metabolómico de los efectos neuroprotectores de la tibolona en un modelo astrocitico humano de lipotoxicidad con ácido palmítico. Colombia - Colciencias International Advisor 2017 - 2020