Permuting input for more effective sampling of 3D conformer space
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SMILES strings and other classic 2D structural formats offer a convenient way to represent molecules as a simplistic connection table, with the inherent advantages of ease of handling and storage. In the context of virtual screening, chemical databases to be screened are often initially represented by canonicalised SMILES strings that can be filtered and pre-processed in a number of ways, resulting in molecules that occupy similar regions of chemical space to active compounds of a therapeutic target. A wide variety of software exists to convert molecules into SMILES format, namely, Mol2smi (Daylight Inc.), MOE (Chemical Computing Group) and Babel (Openeye Scientific Software). Depending on the algorithm employed, the atoms of a SMILES string defining a molecule can be ordered differently. Upon conversion to 3D coordinates they result in the production of ostensibly the same molecule.
In this work we show how different permutations of a SMILES string can affect conformer generation, affecting reliability and repeatability of the results. Furthermore, we propose a novel procedure for the generation of conformers, taking advantage of the permutation of the input strings—both SMILES and other 2D formats, leading to more effective sampling of conformation space in output, and also implementing fingerprint and principal component analyses step to post process and visualise the results.
KeywordsConformers Docking Drug discovery Fingerprints Scoring SMILES Virtual screening
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This work was supported through funding from Science Foundation Ireland and the Irish Health Research Board.
- 3.Bringmann BKA (2004) Frequent SMILES. Lernen, Wissensentdeckung und Adaptivität, Workshop GI Fachgruppe Maschinelles Lernen, part of LWA 2004Google Scholar
- 5.Knox AJS, Meegan MJ, Carta G, Lloyd DG (2005) J Chem Inf Model 45(6):1908–19Google Scholar
- 9.Daylight Chemical Informations Systems Inc. (URL: http://www.daylight.com)Google Scholar
- 10.Molecular Operating Environment (MOE), developed and distributed by Chemical Computing Group (http://wwwchemcompcom)Google Scholar
- 11.Babel v2.0A3, distributed by Openeye Scientific SoftwareGoogle Scholar
- 12.Chemsketch v8.17, www.acdlabs.comGoogle Scholar
- 15.CORINA 3.6, distributed by Molecular Networks GmbHGoogle Scholar
- 16.Cambridge Structural Database, http://www.ccdc.cam.ac.uk/Google Scholar
- 17.OMEGA 1.8.1, distributed by Openeye Scientific SoftwareGoogle Scholar
- 18.Catalyst v4.9.1, www.accelrys.comGoogle Scholar
- 19.RUBICON, distributed by Daylight Chemical Informations Systems IncGoogle Scholar
- 20.Shanno DF, Phua KH (1980) ACM Trans Math Software 6:618Google Scholar
- 23.Ivanciuc O (2003) In: Gasteiger J (ed) Handbook of chemoinformatic , vol. 1. p 103Google Scholar
- 25.Babel 1.100.2, Distributed by Openeye Scientific SoftwareGoogle Scholar
- 26.oechem, RMSD, Distributed by Openeye Scientific SoftwareGoogle Scholar