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Research Topics

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We focus on pharmaceutically relevant metalloenzymes that process DNA and RNA. We are particularly interested in metalloenzymes that are promising new targets for drug discovery.


  • Donati E., Genna V., De Vivo M.
    Recruiting Mechanism and Functional Role of a Third Metal Ion in the Enzymatic Activity of 5′ Structure-Specific Nucleases,
    Journal of the American Chemical Society, 2020
    DOI 10.1021/jacs.9b10656
  • Genna V., Marcia M., De Vivo M.
    A Transient and Flexible Cation-πInteraction Promotes Hydrolysis of Nucleic Acids in DNA and RNA Nucleases
    Journal of the American Chemical Society, 2019
    DOI 10.1021/jacs.9b03663
  • Riccardi L., Genna V., De Vivo M.
    Metal–ligand interactions in drug design
    Nature Reviews Chemistry, 2018
    DOI 10.1038/s41570-018-0018-6

We are interested in using multiscale molecular modeling, docking, free energy perturbation calculations, and machine learning to investigate pharmacologically relevant proteins like GTPases and polymerases. Small molecule inhibitors are designed, synthesized, and tested to act on selected targets. We are intensely working on targets that are essential for cancer-related signaling pathways. From this research line, we launched Alyra Therapeutics.


  • Jahid S., Ortega J.A., Vuong L.M., Acquistapace I.M., Hachey S.J., Flesher J.L., La Serra M.A., Brindani N., La Sala G., Manigrasso J., Arencibia J.M., Bertozzi S.M., Summa M., Bertorelli R., Armirotti A., Jin R., Liu Z., Chen C.-F., Edwards R., Hughes C.C.W., De Vivo M., Ganesan A.K.
    Structure-based design of CDC42 effector interaction inhibitors for the treatment of cancer
    Cell Reports, 2022
    DOI 10.1016/j.celrep.2022.110641
  • La Serra M.A., Vidossich P., Acquistapace I., Ganesan A.K., De Vivo M.
    Alchemical Free Energy Calculations to Investigate Protein-Protein Interactions: the Case of the CDC42/PAK1 Complex
    Journal of Chemical Information and Modeling, 2022
    DOI 10.1021/acs.jcim.2c00348
  • De Vivo M., Masetti M., Bottegoni G., Cavalli A.
    Role of Molecular Dynamics and Related Methods in Drug Discovery
    Journal of Medicinal Chemistry, 2016
    DOI 10.1021/acs.jmedchem.5b01684

We study RNA molecules that are involved in pathophysiological processes, like gene splicing. We integrate multiscale modeling with computer aided design of small molecules targeting RNA. Compounds are synthesized and tested for their pharmacological effect.


  • Marcia M., Manigrasso J., De Vivo M.
    Finding the Ion in the RNA-Stack: Can Computational Models Accurately Predict Key Functional Elements in Large Macromolecular Complexes?
    Journal of Chemical Information and Modeling, 2021
    DOI 10.1021/acs.jcim.1c00572
  • Manigrasso J., Marcia M., De Vivo M.
    Computer-aided design of RNA-targeted small molecules: A growing need in drug discovery
    Chem, 2021
    DOI 10.1016/j.chempr.2021.05.021
  • Manigrasso J., Chillon I., Genna V., Vidossich P., Somarowthu S., Pyle A.M., De Vivo M., Marcia M.
    Visualizing group II intron dynamics between the first and second steps of splicing
    Nature Communications, 2020
    DOI 10.1038/s41467-020-16741-4

We work on the pharmacological intervention to treat cognitive impairment in a number of neurodevelopmental disorders, a currently unmet medical need. To this end, we aim at the functional and structural characterization of pharmaceutically relevant ionic membrane transporters, which are novel targets for therapeutic intervention to treat neurological diseases. From this research line, we launched IAMA Therapeutics.


  • Borgogno M., Savardi A., Manigrasso J., Turci A., Portioli C., Ottonello G., Bertozzi S.M., Armirotti A., Contestabile A., Cancedda L., De Vivo M.
    Design, Synthesis, In Vitro and In Vivo Characterization of Selective NKCC1 Inhibitors for the Treatment of Core Symptoms in down Syndrome
    Journal of Medicinal Chemistry, 2021
    DOI 10.1021/acs.jmedchem.1c00603
  • Savardi A., Borgogno M., De Vivo M., Cancedda L.
    Pharmacological tools to target NKCC1 in brain disorders
    Trends in Pharmacological Sciences, 2021
    DOI 10.1016/j.tips.2021.09.005
  • Savardi A., Borgogno M., Narducci R., La Sala G., Ortega J.A., Summa M., Armirotti A., Bertorelli R., Contestabile A., De Vivo M., Cancedda L.
    Discovery of a Small Molecule Drug Candidate for Selective NKCC1 Inhibition in Brain Disorders
    Chem, 2020
    DOI 10.1016/j.chempr.2020.06.017

The multifunctional nature of gold nanoparticles permits to design and construct artificial systems with precise and efficient functionality. In this regard, we are using atomistic simulations to understand general principles that regulate the dynamical behavior of gold nanoparticles. Insights from these computations are used for the fine-tuning of experimental parameters, moving forward innovative applications of these exciting ultra small objects.


  • Franco-Ulloa S., Riccardi L., Rimembrana F., Grottin E., Pini M., De Vivo M.
    NanoModeler CG: A Tool for Modeling and Engineering Functional Nanoparticles at a Coarse-Grained Resolution
    Journal of Chemical Theory and Computation, 2023
    DOI 10.1021/acs.jctc.2c01029
  • Sun X., Riccardi L., De Biasi F., Rastrelli F., De Vivo M., Mancin F.
    Molecular-Dynamics-Simulation-Directed Rational Design of Nanoreceptors with Targeted Affinity
    Angewandte Chemie - International Edition, 2019
    DOI 10.1002/anie.201902316
  • Riccardi L., Gabrielli L., Sun X., De Biasi F., Rastrelli F., Mancin F., De Vivo M.
    Nanoparticle-Based Receptors Mimic Protein-Ligand Recognition
    Chem, 2017
    DOI 10.1016/j.chempr.2017.05.016