Freely available conformer generation methods: how good are they?
Conformer generation has important implications in cheminformatics, particularly in computational drug discovery where the quality of conformer generation software may affect the outcome of a virtual screening exercise. We examine the performance of four freely available small molecule conformer gen...
| मुख्य लेखकों: | , , |
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| स्वरूप: | Journal article |
| भाषा: | English |
| प्रकाशित: |
2012
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| _version_ | 1826265585500028928 |
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| author | Ebejer, J Morris, G Deane, C |
| author_facet | Ebejer, J Morris, G Deane, C |
| author_sort | Ebejer, J |
| collection | OXFORD |
| description | Conformer generation has important implications in cheminformatics, particularly in computational drug discovery where the quality of conformer generation software may affect the outcome of a virtual screening exercise. We examine the performance of four freely available small molecule conformer generation tools (Balloon, Confab, Frog2, and RDKit) alongside a commercial tool (MOE). The aim of this study is 3-fold: (i) to identify which tools most accurately reproduce experimentally determined structures; (ii) to examine the diversity of the generated conformational set; and (iii) to benchmark the computational time expended. These aspects were tested using a set of 708 drug-like molecules assembled from the OMEGA validation set and the Astex Diverse Set. These molecules have varying physicochemical properties and at least one known X-ray crystal structure. We found that RDKit and Confab are statistically better than other methods at generating low rmsd conformers to the known structure. RDKit is particularly suited for less flexible molecules while Confab, with its systematic approach, is able to generate conformers which are geometrically closer to the experimentally determined structure for molecules with a large number of rotatable bonds (≥10). In our tests RDKit also resulted as the second fastest method after Frog2. In order to enhance the performance of RDKit, we developed a postprocessing algorithm to build a diverse and representative set of conformers which also contains a close conformer to the known structure. Our analysis indicates that, with postprocessing, RDKit is a valid free alternative to commercial, proprietary software. |
| first_indexed | 2024-03-06T20:25:59Z |
| format | Journal article |
| id | oxford-uuid:2f69985c-3e0c-44eb-9136-e4020f9c1ea8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:25:59Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:2f69985c-3e0c-44eb-9136-e4020f9c1ea82022-03-26T12:55:17ZFreely available conformer generation methods: how good are they?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2f69985c-3e0c-44eb-9136-e4020f9c1ea8EnglishSymplectic Elements at Oxford2012Ebejer, JMorris, GDeane, CConformer generation has important implications in cheminformatics, particularly in computational drug discovery where the quality of conformer generation software may affect the outcome of a virtual screening exercise. We examine the performance of four freely available small molecule conformer generation tools (Balloon, Confab, Frog2, and RDKit) alongside a commercial tool (MOE). The aim of this study is 3-fold: (i) to identify which tools most accurately reproduce experimentally determined structures; (ii) to examine the diversity of the generated conformational set; and (iii) to benchmark the computational time expended. These aspects were tested using a set of 708 drug-like molecules assembled from the OMEGA validation set and the Astex Diverse Set. These molecules have varying physicochemical properties and at least one known X-ray crystal structure. We found that RDKit and Confab are statistically better than other methods at generating low rmsd conformers to the known structure. RDKit is particularly suited for less flexible molecules while Confab, with its systematic approach, is able to generate conformers which are geometrically closer to the experimentally determined structure for molecules with a large number of rotatable bonds (≥10). In our tests RDKit also resulted as the second fastest method after Frog2. In order to enhance the performance of RDKit, we developed a postprocessing algorithm to build a diverse and representative set of conformers which also contains a close conformer to the known structure. Our analysis indicates that, with postprocessing, RDKit is a valid free alternative to commercial, proprietary software. |
| spellingShingle | Ebejer, J Morris, G Deane, C Freely available conformer generation methods: how good are they? |
| title | Freely available conformer generation methods: how good are they? |
| title_full | Freely available conformer generation methods: how good are they? |
| title_fullStr | Freely available conformer generation methods: how good are they? |
| title_full_unstemmed | Freely available conformer generation methods: how good are they? |
| title_short | Freely available conformer generation methods: how good are they? |
| title_sort | freely available conformer generation methods how good are they |
| work_keys_str_mv | AT ebejerj freelyavailableconformergenerationmethodshowgoodarethey AT morrisg freelyavailableconformergenerationmethodshowgoodarethey AT deanec freelyavailableconformergenerationmethodshowgoodarethey |