@article{borrel_melander_fourches_2021, title={Cheminformatics Analysis of Fluoroquinolones and Their Inhibition Potency Against Four Pathogens}, volume={40}, ISSN={["1868-1751"]}, DOI={10.1002/minf.202000215}, abstractNote={Drug-resistant bacteria are a worldwide public health concern. As the prevalence of multi-drug resistant pathogens outpaces the discovery of new antibacterials, it is of importance to explore the structure-activity relationships for series of known bactericides with proven scaffolds. Herein, we assembled a set of 507 fluoroquinolone analogues all experimentally tested for their inhibition potency against four pathogens: Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae. We relied on cheminformatics techniques to characterize and cluster them based on their structural similarity and analyzed the structure-activity relationships identified for each cluster of fluoroquinolones. Then, we utilized machine learning techniques to develop and validate predictive QSAR models for computing the inhibition potencies (pMIC) of analogues for each pathogen. These QSAR models afforded reasonable external prediction performances (R2≥0.6, MAE∼0.4). This study confirmed that (i) there are both global and local inter-pathogen concordance regarding the antibacterial potency of fluoroquinolones, (ii) small clusters of fluoroquinolone analogues are characterized by unique patterns of strain selectivity and potency, the latter being potentially useful to design new analogues with enhanced potency and/or selectivity towards a given pathogen, and (iii) robust QSAR models were obtained allowing for future design of new bioactive fluoroquinolones.}, number={5}, journal={MOLECULAR INFORMATICS}, author={Borrel, Alexandre and Melander, Christian and Fourches, Denis}, year={2021}, month={May} }
 @article{zin_borrel_fourches_2020, title={Benchmarking 2D/3D/MD-QSAR Models for Imatinib Derivatives: How Far Can We Predict?}, volume={60}, ISSN={["1549-960X"]}, DOI={10.1021/acs.jcim.0c00200}, abstractNote={Imatinib, a 2-phenylaminopyridine-based BCR-ABL tyrosine kinase inhibitor, is a highly effective drug for treating Chronic Myeloid Leukemia (CML). However, cases of drug resistance are constantly e...}, number={7}, journal={JOURNAL OF CHEMICAL INFORMATION AND MODELING}, author={Zin, Phyo Phyo Kyaw and Borrel, Alexandre and Fourches, Denis}, year={2020}, month={Jul}, pages={3342–3360} }
 @article{borrel_kleinstreuer_fourches_2018, title={Exploring drug space with ChemMaps.com}, volume={34}, ISSN={["1460-2059"]}, DOI={10.1093/bioinformatics/bty412}, abstractNote={Easily navigating chemical space has become more important due to the increasing size and diversity of publicly-accessible databases such as DrugBank, ChEMBL or Tox21. To do so, modelers typically rely on complex projection techniques using molecular descriptors computed for all the chemicals to be visualized. However, the multiple cheminformatics steps required to prepare, characterize, compute and explore those molecules, are technical, typically necessitate scripting skills, and thus represent a real obstacle for non-specialists.We developed the ChemMaps.com webserver to easily browse, navigate and mine chemical space. The first version of ChemMaps.com features more than 8000 approved, in development, and rejected drugs, as well as over 47 000 environmental chemicals.The webserver is freely available at http://www.chemmaps.com.}, number={21}, journal={BIOINFORMATICS}, author={Borrel, Alexandre and Kleinstreuer, Nicole C. and Fourches, Denis}, year={2018}, month={Nov}, pages={3773–3775} }
 @article{borrel_fourches_2017, title={RealityConvert: a tool for preparing 3D models of biochemical structures for augmented and virtual reality}, volume={33}, ISSN={["1460-2059"]}, DOI={10.1093/bioinformatics/btx485}, abstractNote={There is a growing interest for the broad use of Augmented Reality (AR) and Virtual Reality (VR) in the fields of bioinformatics and cheminformatics to visualize complex biological and chemical structures. AR and VR technologies allow for stunning and immersive experiences, offering untapped opportunities for both research and education purposes. However, preparing 3D models ready to use for AR and VR is time-consuming and requires a technical expertise that severely limits the development of new contents of potential interest for structural biologists, medicinal chemists, molecular modellers and teachers.Herein we present the RealityConvert software tool and associated website, which allow users to easily convert molecular objects to high quality 3D models directly compatible for AR and VR applications. For chemical structures, in addition to the 3D model generation, RealityConvert also generates image trackers, useful to universally call and anchor that particular 3D model when used in AR applications. The ultimate goal of RealityConvert is to facilitate and boost the development and accessibility of AR and VR contents for bioinformatics and cheminformatics applications.http://www.realityconvert.com.dfourch@ncsu.edu.Supplementary data are available at Bioinformatics online.}, number={23}, journal={BIOINFORMATICS}, author={Borrel, Alexandre and Fourches, Denis}, year={2017}, month={Dec}, pages={3816–3818} }
 @article{zhang_borrel_ghemtio_regad_gennas_camproux_yli-kauhaluoma_xhaard_2017, title={Structural Isosteres of Phosphate Groups in the Protein Data Bank}, volume={57}, ISSN={["1549-960X"]}, DOI={10.1021/acs.jcim.6b00519}, abstractNote={We developed a computational workflow to mine the Protein Data Bank for isosteric replacements that exist in different binding site environments but have not necessarily been identified and exploited in compound design. Taking phosphate groups as examples, the workflow was used to construct 157 data sets, each composed of a reference protein complexed with AMP, ADP, ATP, or pyrophosphate as well other ligands. Phosphate binding sites appear to have a high hydration content and large size, resulting in U-shaped bioactive conformations recurrently found across unrelated protein families. A total of 16 413 replacements were extracted, filtered for a significant structural overlap on phosphate groups, and sorted according to their SMILES codes. In addition to the classical isosteres of phosphate, such as carboxylate, sulfone, or sulfonamide, unexpected replacements that do not conserve charge or polarity, such as aryl, aliphatic, or positively charged groups, were found.}, number={3}, journal={JOURNAL OF CHEMICAL INFORMATION AND MODELING}, author={Zhang, Yuezhou and Borrel, Alexandre and Ghemtio, Leo and Regad, Leslie and Gennas, Gustav Boije and Camproux, Anne-Claude and Yli-Kauhaluoma, Jan and Xhaard, Henri}, year={2017}, month={Mar}, pages={499–516} }