A comparison between 2D and 3D descriptors in QSAR modeling based on bio‐active conformations
QSAR models are widely and successfully used in many research areas. The success of such models highly depends on molecular descriptors typically classified as 1D, 2D, 3D, or 4D. While 3D information is likely important, e. g., for modeling ligand‐protein binding, previous comparisons between the pe...
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Published in | Molecular informatics Vol. 42; no. 4; pp. e2200186 - n/a |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Germany
Wiley Subscription Services, Inc
01.04.2023
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Subjects | |
Online Access | Get full text |
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Summary: | QSAR models are widely and successfully used in many research areas. The success of such models highly depends on molecular descriptors typically classified as 1D, 2D, 3D, or 4D. While 3D information is likely important, e. g., for modeling ligand‐protein binding, previous comparisons between the performances of 2D and 3D descriptors were inconclusive. Yet in such comparisons the modeled ligands were not necessarily represented by their bioactive conformations. With this in mind, we mined the PDB for sets of protein‐ligand complexes sharing the same protein for which uniform activity data were reported. The results, totaling 461 structures spread across six series were compiled into a carefully curated, first of its kind dataset in which each ligand is represented by its bioactive conformation. Next, each set was characterized by 2D, 3D and 2D + 3D descriptors and modeled using three machine learning algorithms, namely, k‐Nearest Neighbors, Random Forest and Lasso Regression. Models’ performances were evaluated on external test sets derived from the parent datasets either randomly or in a rational manner. We found that many more significant models were obtained when combining 2D and 3D descriptors. We attribute these improvements to the ability of 2D and 3D descriptors to code for different, yet complementary molecular properties. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1868-1743 1868-1751 |
DOI: | 10.1002/minf.202200186 |