Bibliography of computer-aided Drug Design

Updated on 7/18/2014. Currently 2130 references

Ligand design / Web services

2013 / 2011 / 2010 /


  • SwissBioisostere: a database of molecular replacements for ligand design.
    Wirth, Matthias and Zoete, Vincent and Michielin, Olivier and Sauer, Wolfgang H B
    Nucleic acids research, 2013, 41(D1), D1137-43
    PMID: 23161688     doi: 10.1093/nar/gks1059
    The SwissBioisostere database ( contains information on molecular replacements and their performance in biochemical assays. It is meant to provide researchers in drug discovery projects with ideas for bioisosteric modifications of their current lead molecule, as well as to give interested scientists access to the details on particular molecular replacements. As of August 2012, the database contains 21 293 355 datapoints corresponding to 5 586 462 unique replacements that have been measured in 35 039 assays against 1948 molecular targets representing 30 target classes. The accessible data were created through detection of matched molecular pairs and mining bioactivity data in the ChEMBL database. The SwissBioisostere database is hosted by the Swiss Institute of Bioinformatics and available via a web-based interface.


  • FragmentStore-a comprehensive database of fragments linking metabolites, toxic molecules and drugs.
    Ahmed, Jessica and Worth, Catherine L and Thaben, Paul and Matzig, Christian and Blasse, Corinna and Dunkel, Mathias and Preissner, Robert
    Nucleic acids research, 2011, 39(Database issue), D1049-54
    PMID: 20965964     doi: 10.1093/nar/gkq969
    Consideration of biomolecules in terms of their molecular building blocks provides valuable new information regarding their synthesis, degradation and similarity. Here, we present the FragmentStore, a resource for the comparison of fragments found in metabolites, drugs or toxic compounds. Starting from 13,000 metabolites, 16,000 drugs and 2200 toxic compounds we generated 35,000 different building blocks (fragments), which are not only relevant to their biosynthesis and degradation but also provide important information regarding side-effects and toxicity. The FragmentStore provides a variety of search options such as 2D structure, molecular weight, rotatable bonds, etc. Various analysis tools have been implemented including the calculation of amino acid preferences of fragments' binding sites, classification of fragments based on the enzyme classification class of the enzyme(s) they bind to and small molecule library generation via a fragment-assembler tool. Using the FragmentStore, it is now possible to identify the common fragments of different classes of molecules and generate hypotheses about the effects of such intersections. For instance, the co-occurrence of fragments in different drugs may indicate similar targets and possible off-target interactions whereas the co-occurrence of fragments in a drug and a toxic compound/metabolite could be indicative of side-effects. The database is publicly available at:

  • iScreen: world's first cloud-computing web server for virtual screening and de novo drug design based on TCM database@Taiwan
    Tsai, Tsung-Ying and Chang, Kai-Wei and Chen, Calvin Yu-Chian
    Journal of computer-aided molecular design, 2011, 25(6), 525-531
    PMID: 21647737     doi: 10.1007/s10822-011-9438-9
    The rapidly advancing researches on traditional Chinese medicine (TCM) have greatly intrigued pharmaceutical industries worldwide. To take initiative in the next generation of drug development, we constructed a cloud-computing system for TCM intelligent screening system (iScreen) based on TCM Database@Taiwan. iScreen is compacted web server for TCM docking and followed by customized de novo drug design. We further implemented a protein preparation tool that both extract protein of interest from a raw input file and estimate the size of ligand bind site. In addition, iScreen is designed in user-friendly graphic interface for users who have less experience with the command line systems. For customized docking, multiple docking services, including standard, in-water, pH environment, and flexible docking modes are implemented. Users can download first 200 TCM compounds of best docking results. For TCM de novo drug design, iScreen provides multiple molecular descriptors for a user's interest. iScreen is the world's first web server that employs world's largest TCM database for virtual screening and de novo drug design. We believe our web server can lead TCM research to a new era of drug development. The TCM docking and screening server is available at


  • e-LEA3D: a computational-aided drug design web server.
    Douguet, Dominique
    Nucleic acids research, 2010, 38(Web Server issue), W615-21
    PMID: 20444867     doi: 10.1093/nar/gkq322
    e-LEA3D web server integrates three complementary tools to perform computer-aided drug design based on molecular fragments. In drug discovery projects, there is a considerable interest in identifying novel and diverse molecular scaffolds to enhance chances of success. The de novo drug design tool is used to invent new ligands to optimize a user-specified scoring function. The composite scoring function includes both structure- and ligand-based evaluations. The de novo approach is an alternative to a blind virtual screening of large compound collections. A heuristic based on a genetic algorithm rapidly finds which fragments or combination of fragments fit a QSAR model or the binding site of a protein. While the approach is ideally suited for scaffold-hopping, this module also allows a scan for possible substituents to a user-specified scaffold. The second tool offers a traditional virtual screening and filtering of an uploaded library of compounds. The third module addresses the combinatorial library design that is based on a user-drawn scaffold and reactants coming, for example, from a chemical supplier. The e-LEA3D server is available at: