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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Chan SL, Labute P (2010) Training a scoring function for the alignment of small molecules. J Chem Inf Model 50:1724–1735
Lemmen C, Lengauer T (2000) Computational methods for the structural alignment of molecules. J Comput Aided Mol Des 14:215–232
Leach AR, Gillet VJ, Lewis RA, Taylor R (2010) Three-dimensional pharmacophore methods in drug discovery. J Med Chem 53:539–558
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
Vainio MJ, Santeri Puranen J, Johnson MS (2009) ShaEP: molecular overlay based on shape and electrostatic potential. J Chem Inf Model 49:492–502
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
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
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
Van Drie JH (2010) History of 3D pharmacophore searching: commercial, academic and open-source tools. Drug Disc Today 7:e255–e262
Taminau J, Thijs G, De Winter H (2008) Pharao: pharmacophore alignment and optimization. J Mol Graph Model 27:161–169
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
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
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
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
TINKER—Software tools for molecular design, version 5.1; http://dasher.wustl.edu/tinker/. Accessed 13 June 2011
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
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
MOE 2010.10; Chemical Computing Group Inc., Montreal, Quebec, Canada, 2010
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
Richmond NJ, Willett P, Clark RD (2004) Alignment of three-dimensional molecules using an image recognition algorithm. J Mol Graph Model 23:199–209
Jonker R, Volgenant A (1987) A shortest augmenting path algorithm for dense and sparse linear assignment problems. Computing 38:325–340
Kearsley SK (1989) On the orthogonal transformation used for structural comparisons. Acta Cryst A45:208–210
Petitjean M (1998) Interactive maximal common 3D substructure searching with the combined SDM/RMS algorithm. Computers Chem 22:463–465
Sutherland JJ, O’Brien LA, Weaver DF (2004) A comparison of methods for modeling quantitative structure—activity relationships. J Med Chem 47:5541–5554
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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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