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Open3DALIGN: an open-source software aimed at unsupervised ligand alignment

Abstract

An open-source, cross-platform software aimed at conformer generation and unsupervised rigid-body molecular alignment is presented. Different algorithms have been implemented to perform single and multi-conformation superimpositions on one or more templates. Alignments can be accomplished by matching pharmacophores, heavy atoms or a combination of the two. All methods have been successfully validated on eight comprehensive datasets previously gathered by Sutherland and co-workers. High computational performance has been attained through efficient parallelization of the code. The unsupervised nature of the alignment algorithms, together with its scriptable interface, make Open3DALIGN an ideal component of high-throughput, automated cheminformatics workflows.

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References

  1. 1.

    Chan SL, Labute P (2010) Training a scoring function for the alignment of small molecules. J Chem Inf Model 50:1724–1735

  2. 2.

    Lemmen C, Lengauer T (2000) Computational methods for the structural alignment of molecules. J Comput Aided Mol Des 14:215–232

  3. 3.

    Leach AR, Gillet VJ, Lewis RA, Taylor R (2010) Three-dimensional pharmacophore methods in drug discovery. J Med Chem 53:539–558

  4. 4.

    Rönkkö T, Tervo AJ, Parkkinen J, Poso A (2006) BRUTUS: optimization of a grid-based similarity function for rigid-body molecular superposition. II. Description and characterization. J Comput Aided Mol Des 20:227–236

  5. 5.

    Vainio MJ, Santeri Puranen J, Johnson MS (2009) ShaEP: molecular overlay based on shape and electrostatic potential. J Chem Inf Model 49:492–502

  6. 6.

    Güner O, Clement O, Kurogi Y (2004) Pharmacophore modeling and three dimensional database searching for drug design using Catalyst: recent advances. Curr Med Chem 11:2991–3005

  7. 7.

    Dixon SL, Smondyrev AM, Knoll EH, Rao SN, Shaw DE, Friesner RA (2006) PHASE: a new engine for pharmacophore perception, 3D QSAR model development, and 3D database screening: 1. Methodology and preliminary results. J Comput Aided Mol Des 20:647–671

  8. 8.

    Richmond NJ, Abrams CA, Wolohan PRN, Abrahamian E, Willett P, Clark RD (2006) GALAHAD: 1. Pharmacophore identification by hypermolecular alignment of ligands in 3D. J Comput Aided Mol Des 20:567–587

  9. 9.

    Van Drie JH (2010) History of 3D pharmacophore searching: commercial, academic and open-source tools. Drug Disc Today 7:e255–e262

  10. 10.

    Taminau J, Thijs G, De Winter H (2008) Pharao: pharmacophore alignment and optimization. J Mol Graph Model 27:161–169

  11. 11.

    Steinbeck C, Hoppe C, Kuhn S, Floris M, Guha R, Willighagen EL (2006) Recent developments of the chemistry development kit (CDK)—an open-source java library for chemo- and bioinformatics. Curr Pharm Des 12:2111–2120

  12. 12.

    Tosco P, Balle T (2011) Open3DGRID: an open-source software aimed at high-throughput generation of molecular interaction fields (MIFs); http://open3dgrid.org/. Accessed 13 June 2011

  13. 13.

    Tosco P, Balle T (2011) Open3DQSAR: a new open-source software aimed at high-throughput chemometric analysis of molecular interaction fields. J Mol Model 17: 201–208; http://open3dqsar.org/. Accessed 13 June 2011

  14. 14.

    O’Connor SD, Smith PE, al-Obeidi F, Pettitt BM (1992) Quenched molecular dynamics simulations of tuftsin and proposed cyclic analogs. J Med Chem 35:2870–2881

  15. 15.

    TINKER—Software tools for molecular design, version 5.1; http://dasher.wustl.edu/tinker/. Accessed 13 June 2011

  16. 16.

    Tosco P, Balle T, Shiri F (2011) SDF2XYZ2SDF: how to exploit TINKER power in chemoinformatics projects. J Mol Model. Doi:10.1007/s00894-011-1111-7; http://sdf2xyz2sdf.sourceforge.net/. Accessed 13 June 2011

  17. 17.

    Guha R, Howard MT, Hutchison GR, Murray-Rust P, Rzepa H, Steinbeck C, Wegner JK, Willighagen E (2006) The Blue Obelisk—Interoperability in chemical informatics. J Chem Inf Model 46:991–998

  18. 18.

    MOE 2010.10; Chemical Computing Group Inc., Montreal, Quebec, Canada, 2010

  19. 19.

    Kirchmair J, Wolber G, Laggner C, Langer T (2006) Comparative performance assessment of the conformational model generators Omega and Catalyst: a large-scale survey on the retrieval of protein-bound ligand conformations. J Chem Inf Model 46:1848–1861

  20. 20.

    Richmond NJ, Willett P, Clark RD (2004) Alignment of three-dimensional molecules using an image recognition algorithm. J Mol Graph Model 23:199–209

  21. 21.

    Jonker R, Volgenant A (1987) A shortest augmenting path algorithm for dense and sparse linear assignment problems. Computing 38:325–340

  22. 22.

    Kearsley SK (1989) On the orthogonal transformation used for structural comparisons. Acta Cryst A45:208–210

  23. 23.

    Petitjean M (1998) Interactive maximal common 3D substructure searching with the combined SDM/RMS algorithm. Computers Chem 22:463–465

  24. 24.

    Sutherland JJ, O’Brien LA, Weaver DF (2004) A comparison of methods for modeling quantitative structure—activity relationships. J Med Chem 47:5541–5554

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Acknowledgments

We are grateful to the developers of OpenBabel, Pharao and TINKER, on which Open3DALIGN depends to do its job, and to an anonymous reviewer who contributed to improve this manuscript. We acknowledge the support of Chemical Computing Group. Part of this work was carried out by P.T. at the University of Copenhagen under a visiting scientist grant supported by the Drug Research Academy (DRA). T.B. was supported by grants from the Lundbeck Foundation. Part of this work was carried out by F.S. at the University of Turin under a visiting scientist grant.

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Correspondence to Paolo Tosco.

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Tosco, P., Balle, T. & Shiri, F. Open3DALIGN: an open-source software aimed at unsupervised ligand alignment. J Comput Aided Mol Des 25, 777 (2011). https://doi.org/10.1007/s10822-011-9462-9

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Keywords

  • Cheminformatics
  • Alignment
  • Superposition
  • Pharmacophore