Dataset Information

Greedy 3-Point Search (G3PS)-A Novel Algorithm for Pharmacophore Alignment.

ABSTRACT: Chemical features of small molecules can be abstracted to 3D pharmacophore models, which are easy to generate, interpret, and adapt by medicinal chemists. Three-dimensional pharmacophores can be used to efficiently match and align molecules according to their chemical feature pattern, which facilitates the virtual screening of even large compound databases. Existing alignment methods, used in computational drug discovery and bio-activity prediction, are often not suitable for finding matches between pharmacophores accurately as they purely aim to minimize RMSD or maximize volume overlap, when the actual goal is to match as many features as possible within the positional tolerances of the pharmacophore features. As a consequence, the obtained alignment results are often suboptimal in terms of the number of geometrically matched feature pairs, which increases the false-negative rate, thus negatively affecting the outcome of virtual screening experiments. We addressed this issue by introducing a new alignment algorithm, Greedy 3-Point Search (G3PS), which aims at finding optimal alignments by using a matching-feature-pair maximizing search strategy while at the same time being faster than competing methods.

SUBMITTER: Permann C

PROVIDER: S-EPMC8658842 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Greedy 3-Point Search (G3PS)-A Novel Algorithm for Pharmacophore Alignment.

Permann Christian C Seidel Thomas T Langer Thierry T

Molecules (Basel, Switzerland) 20211127 23

Chemical features of small molecules can be abstracted to 3D pharmacophore models, which are easy to generate, interpret, and adapt by medicinal chemists. Three-dimensional pharmacophores can be used to efficiently match and align molecules according to their chemical feature pattern, which facilitates the virtual screening of even large compound databases. Existing alignment methods, used in computational drug discovery and bio-activity prediction, are often not suitable for finding matches bet ...[more]

PMID: 34885781

Similar Datasets

Project description:BackgroundCophylogeny mapping is used to uncover deep coevolutionary associations between two or more phylogenetic histories at a macro coevolutionary scale. As cophylogeny mapping is NP-Hard, this technique relies heavily on heuristics to solve all but the most trivial cases. One notable approach utilises a metaheuristic to search only a subset of the exponential number of fixed node orderings possible for the phylogenetic histories in question. This is of particular interest as it is the only known heuristic that guarantees biologically feasible solutions. This has enabled research to focus on larger coevolutionary systems, such as coevolutionary associations between figs and their pollinator wasps, including over 200 taxa. Although able to converge on solutions for problem instances of this size, a reduction from the current cubic running time is required to handle larger systems, such as Wolbachia and their insect hosts.ResultsRather than solving this underlying problem optimally this work presents a greedy algorithm called TreeCollapse, which uses common topological patterns to recover an approximation of the coevolutionary history where the internal node ordering is fixed. This approach offers a significant speed-up compared to previous methods, running in linear time. This algorithm has been applied to over 100 well-known coevolutionary systems converging on Pareto optimal solutions in over 68% of test cases, even where in some cases the Pareto optimal solution has not previously been recoverable. Further, while TreeCollapse applies a local search technique, it can guarantee solutions are biologically feasible, making this the fastest method that can provide such a guarantee.ConclusionAs a result, we argue that the newly proposed algorithm is a valuable addition to the field of coevolutionary research. Not only does it offer a significantly faster method to estimate the cost of cophylogeny mappings but by using this approach, in conjunction with existing heuristics, it can assist in recovering a larger subset of the Pareto front than has previously been possible.

Dataset Information

Greedy 3-Point Search (G3PS)-A Novel Algorithm for Pharmacophore Alignment.

Publications

Greedy 3-Point Search (G3PS)-A Novel Algorithm for Pharmacophore Alignment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets