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Terminated line: Drug design

The research line on structure-based drug design was initiated by Ángel Ramirez Ortíz when he was in the laboratory of Prof. Federico Gago in Alcalá de Henares Universtiy. After Ángel passed away, this line was directed by Dr. Antonio Morreale, a researcher with a strong experience in the field. This line terminated when Dr. Morreale left the group at the beginning of 2013, but the software that it generated is still available, although not anymore maintained. Among this software, it has to be mentioned an integrated computational platform to perform massive Virtual Screening (VS) experiments, which allow to extract the most promising candidates able to interact with a protein of clinical interest from large databases of small molecules . This Virtual Screening Data Management on an Integrated Platform (VSDMIP) has been proved to be an useful tool for developing new methods, and it generated several patents in collaboration with experimental groups.

Another area in medical chemistry that was of interest of the research group directed by Ángel Ramirez Ortíz and subsequently by Antonio Morreale was 3D-QSAR (3-Dimensional Quantitative Structure-Activity Relationships). In this regard, the group developed gCOMBINE, a Java-written graphical user interface (GUI) for performing COMparative BINding Energy (COMBINE) analysis on a set of ligand-receptor complexes that allows predicting QSAR, with the aim to understand the molecular basis of specificity of ligand-receptor binding affinities and to guide molecular modifications that improve binding affinity and/or selectivity.

Publications on drug design:

Selected:

  • Klett J, Núñez-Salgado A, Dos Santos HG, Cortés-Cabrera A, Perona A, Gil-Redondo R, Abia D, Gago F, Morreale A. MM-ISMSA: an ultra-fast and accurate scoring function for protein-protein docking. J. Chem. Theory Comput., 8, 3395-3408 (2012) [Pubmed]

  • Cortés Cabrera A, Klett J, Dos Santos HG, Perona A, Gil-Redondo R, Francis SM, Priego EM, Gago F, Morreale A. CRDOCK: An Ultrafast Multipurpose Protein−Ligand Docking Tool. J. Chem. Inf. Model., 52, 2300-20309 (2012)[Pubmed]

  • Cortés-Cabrera A, Gil-Redondo R, Perona A, Gago F, Morreale A. VSDMIP 1.5: an automated structure- and ligand-based virtual screening platform with a PyMOL graphical user interface. J. Comput.-Aided Mol. Design, 25, 813-824 (2011) [Pubmed]

  • Gil-Redondo R, Klett J, Gago F, Morreale A. gCOMBINE: A graphical user interface to perform structure-based comparative binding energy (COMBINE) analysis on a set of ligand-receptor complexes. Proteins. 2010 Jan;78(1):162-72. [Pubmed]

  • Morreale, A.; Gil-Redondo, R.; Ortiz, A.R. A new implicit solvent model for protein-ligand docking. Proteins 2007 May, 67: 606-16. [Pubmed] [PDF] [Material suplementario]

  • Murcia, M.; Morreale, A.; Ortiz, A.R. Comparative Binding Energy Analysis Considering Multiple Receptors: A Step toward 3D-QSAR Models for Multiple Targets. J.Med.Chem. 2006 Oct 19; 49 (21): 6241-53. [Pubmed] [PDF] [Material suplementario]

  • All publications on protein folding and evolution

    Software on drug_design

    Software Index

    VSDMIP

    VSDMIP is a platform for virtual screening (VS) of chemical libraries, integrated within a MySQL relational database.

    • Version : 1.0
    • License : The software is freely distributed for academic and research purposes upon request to the authors.
    • Contact : Antonio Morreale (antonio.morreale@repsol.com)
    • Access : Here
    • References :
      1. Gil-Redondo R, Estrada J, Morreale A, Herranz F, Sancho J, Ortíz AR. VSDMIP: Virtual Screening Data Management on an Integrated Platform J. Comput.-Aided Mol. Design, 23, 171-184 (2009);
      2. Cortés-Cabrera A, Gil-Redondo R, Perona A, Gago F, Morreale A. VSDMIP 1.5: an automated structure- and ligand-based virtual screening platform with a PyMOL graphical user interface. J. Comput.-Aided Mol. Design, 25, 813-824 (2011)[Pubmed]

    CRDOCK

    CRDOCK is a protein-ligand docking program similar to Glide, DOCK or Autodock. It uses a hybrid scoring function based on GlideScore(tm) using a molecular mechanics energy function (AMBER-like) and the ChemScore function to score interactions. The docking program is particularly well suited to generate molecular models of ligand-receptor complexes for further use in COMBINE analysis.

    • Version : 0.8
    • Access : Here.
    • Contact : Antonio Morreale(antonio.morreale@repsol.com)
    • References : Cabrera, A.C.; Klett, J.; Dos Santos, H. G.; Perona, A.; Gil-Redondo, R.; Francis, S. M.; Priegos, E. M.; Gago, F.; Morreale, A.; CRDOCK: An Ultrafast Multipurpose Protein–Ligand Docking Tool (2012) J. Chem. Inf. Model., 52, 2300-20309 (2012)[Pubmed]

    MM-ISMSA

    A Scoring Function for Protein-Protein and Protein-Ligand Docking and Molecular Dynamics.

    • Version : 0.8
    • Access : Here.
    • Contact : ub@cbm.uam.es
    • References :
      1. Klett J, Núñez-Salgado A, Dos Santos HG, Cortés-Cabrera A, Perona A, Gil-Redondo R, Abia D, Gago F, Morreale A. MM-ISMSA: an ultra-fast and accurate scoring function for protein-protein docking. J. Chem. Theory Comput., 8, 3395-3408 (2012) [Pubmed]

      2. Morreale, A.; Gil-Redondo, R.; Ortiz, A.R. A new implicit solvent model for protein-ligand docking. Proteins 2007 May, 67: 606-16.

    gCOMBINE

    A graphical user interface to perform structure-based comparative binding energy (COMBINE) analysis on a set of ligand-receptor complexes.

    • Version : 1.2
    • Access : Here.
    • Contact : ub@cbm.uam.es
    • References :
      1. A graphical user interface to perform structure-based comparative binding energy (COMBINE) analysis on a set of ligand-receptor complexes. Gil-Redondo R,Klett J, Gago F, Morreale A. Proteins 2010; 78(1):162-72
      2. Prediction of drug binding affinities by comparative binding energy analysis. Ortiz AR, Pisabarro MT, Gago F, Wade RC. J Med Chem 1995; 38:2681-91.
      3. Comparative binding energy analysis of HIV-1 protease inhibitors: incorporation of solvent effects and validation as a powerful tool in receptor-based drug design. Perez C, Pastor M, Ortiz AR, Gago F. J Med Chem. 1998:41(6):836-52

    cGRILL: a simple affinity map generator

    cGRILL calculates 4 affinity maps: lipophilic (CH3), hydrogen bond acceptor (=O), hydrogen bond donor (NH4+) and mixed hydrogen bond donor-acceptor (OH). It implements AMBER force field van der Waals and electrostatic terms and a custom hydrogen bond. The code is not pretty but it is licensed under GPL v3.

    Web design: Alfonso Núñez Salgado