Dataset Information

Incorporating Target-Specific Pharmacophoric Information into Deep Generative Models for Fragment Elaboration.

ABSTRACT: Despite recent interest in deep generative models for scaffold elaboration, their applicability to fragment-to-lead campaigns has so far been limited. This is primarily due to their inability to account for local protein structure or a user's design hypothesis. We propose a novel method for fragment elaboration, STRIFE, that overcomes these issues. STRIFE takes as input fragment hotspot maps (FHMs) extracted from a protein target and processes them to provide meaningful and interpretable structural information to its generative model, which in turn is able to rapidly generate elaborations with complementary pharmacophores to the protein. In a large-scale evaluation, STRIFE outperforms existing, structure-unaware, fragment elaboration methods in proposing highly ligand-efficient elaborations. In addition to automatically extracting pharmacophoric information from a protein target's FHM, STRIFE optionally allows the user to specify their own design hypotheses.

SUBMITTER: Hadfield TE

PROVIDER: S-EPMC9131447 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Incorporating Target-Specific Pharmacophoric Information into Deep Generative Models for Fragment Elaboration.

Hadfield Thomas E TE Imrie Fergus F Merritt Andy A Birchall Kristian K Deane Charlotte M CM

Journal of chemical information and modeling 20220502 10

Despite recent interest in deep generative models for scaffold elaboration, their applicability to fragment-to-lead campaigns has so far been limited. This is primarily due to their inability to account for local protein structure or a user's design hypothesis. We propose a novel method for fragment elaboration, STRIFE, that overcomes these issues. STRIFE takes as input fragment hotspot maps (FHMs) extracted from a protein target and processes them to provide meaningful and interpretable structu ...[more]

PMID: 35499971

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Project description:Common visual features used in target tracking, including colour and grayscale, are prone to failure in a confusingly similar-looking background. As the technology of three-dimensional visual information acquisition has gradually gained ground in recent years, the conditions for the wide use of depth information in target tracking has been made available. This study focuses on discussing the possible ways to introduce depth information into the generative target tracking methods based on a kernel density estimation as well as the performance of different methods of introduction, thereby providing a reference for the use of depth information in actual target tracking systems. First, an analysis of the mean-shift technical framework, a typical algorithm used for generative target tracking, is described, and four methods of introducing the depth information are proposed, i.e., the thresholding of the data source, thresholding of the density distribution of the dataset applied, weighting of the data source, and weighting of the density distribution of the dataset. Details of an experimental study conducted to evaluate the validity, characteristics, and advantages of each method are then described. The experimental results showed that the four methods can improve the validity of the basic method to a certain extent and meet the requirements of real-time target tracking in a confusingly similar background. The method of weighting the density distribution of the dataset, into which depth information is introduced, is the prime choice in engineering practise because it delivers an excellent comprehensive performance and the highest level of accuracy, whereas methods such as the thresholding of both the data sources and the density distribution of the dataset are less time-consuming. The performance in comparison with that of a state-of-the-art tracker further verifies the practicality of the proposed approach. Finally, the research results also provide a reference for improvements in other target tracking methods in which depth information can be introduced.

Dataset Information

Incorporating Target-Specific Pharmacophoric Information into Deep Generative Models for Fragment Elaboration.

Publications

Incorporating Target-Specific Pharmacophoric Information into Deep Generative Models for Fragment Elaboration.

Similar Datasets

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