fragSMILES as a chemical string notation for advanced fragment and chirality representation
Abstract Generative models have revolutionized de novo drug design, allowing to produce molecules on-demand with desired physicochemical and pharmacological properties. String based molecular representations, such as SMILES (Simplified Molecular Input Line Entry System) and SELFIES (Self-Referencing...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-025-01423-3 |
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| author | Fabrizio Mastrolorito Fulvio Ciriaco Maria Vittoria Togo Nicola Gambacorta Daniela Trisciuzzi Cosimo Damiano Altomare Nicola Amoroso Francesca Grisoni Orazio Nicolotti |
| author_facet | Fabrizio Mastrolorito Fulvio Ciriaco Maria Vittoria Togo Nicola Gambacorta Daniela Trisciuzzi Cosimo Damiano Altomare Nicola Amoroso Francesca Grisoni Orazio Nicolotti |
| author_sort | Fabrizio Mastrolorito |
| collection | DOAJ |
| description | Abstract Generative models have revolutionized de novo drug design, allowing to produce molecules on-demand with desired physicochemical and pharmacological properties. String based molecular representations, such as SMILES (Simplified Molecular Input Line Entry System) and SELFIES (Self-Referencing Embedded Strings), have played a pivotal role in the success of generative approaches, thanks to their capacity to encode atom- and bond- information and ease-of-generation. However, such ‘atom-level’ string representations could have certain limitations, in terms of capturing information on chirality, and synthetic accessibility of the corresponding designs. In this paper, we present fragSMILES, a novel fragment-based molecular representation in the form of string. fragSMILES encode fragments in a ‘chemically-meaningful’ way via a novel graph-reduction approach, allowing to obtain an efficient, interpretable, and expressive molecular representation, which also avoids fragment redundancy. fragSMILES contributes to the field of fragment-based representation, by reporting fragments and their ‘breaking’ bonds independently. Moreover, fragSMILES also embeds information of molecular chirality, thereby overcoming known limitations of existing string notations. When compared with SMILES, SELFIES and t-SMILES for de novo design, the fragSMILES notation showed its promise in generating molecules with desirable biochemical and scaffolds properties. |
| format | Article |
| id | doaj-art-45fcfa52f2264eccab57c9a6d6953078 |
| institution | Kabale University |
| issn | 2399-3669 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj-art-45fcfa52f2264eccab57c9a6d69530782025-02-02T12:12:15ZengNature PortfolioCommunications Chemistry2399-36692025-01-01811910.1038/s42004-025-01423-3fragSMILES as a chemical string notation for advanced fragment and chirality representationFabrizio Mastrolorito0Fulvio Ciriaco1Maria Vittoria Togo2Nicola Gambacorta3Daniela Trisciuzzi4Cosimo Damiano Altomare5Nicola Amoroso6Francesca Grisoni7Orazio Nicolotti8Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo MoroDipartimento di Chimica, Università degli Studi di Bari Aldo MoroDipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo MoroDipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo MoroDipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo MoroDipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo MoroDipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo MoroInstitute for Complex Molecular Systems and Eindhoven Artificial Intelligence Systems Institute, Department of Biomedical Engineering, Eindhoven University of TechnologyDipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari Aldo MoroAbstract Generative models have revolutionized de novo drug design, allowing to produce molecules on-demand with desired physicochemical and pharmacological properties. String based molecular representations, such as SMILES (Simplified Molecular Input Line Entry System) and SELFIES (Self-Referencing Embedded Strings), have played a pivotal role in the success of generative approaches, thanks to their capacity to encode atom- and bond- information and ease-of-generation. However, such ‘atom-level’ string representations could have certain limitations, in terms of capturing information on chirality, and synthetic accessibility of the corresponding designs. In this paper, we present fragSMILES, a novel fragment-based molecular representation in the form of string. fragSMILES encode fragments in a ‘chemically-meaningful’ way via a novel graph-reduction approach, allowing to obtain an efficient, interpretable, and expressive molecular representation, which also avoids fragment redundancy. fragSMILES contributes to the field of fragment-based representation, by reporting fragments and their ‘breaking’ bonds independently. Moreover, fragSMILES also embeds information of molecular chirality, thereby overcoming known limitations of existing string notations. When compared with SMILES, SELFIES and t-SMILES for de novo design, the fragSMILES notation showed its promise in generating molecules with desirable biochemical and scaffolds properties.https://doi.org/10.1038/s42004-025-01423-3 |
| spellingShingle | Fabrizio Mastrolorito Fulvio Ciriaco Maria Vittoria Togo Nicola Gambacorta Daniela Trisciuzzi Cosimo Damiano Altomare Nicola Amoroso Francesca Grisoni Orazio Nicolotti fragSMILES as a chemical string notation for advanced fragment and chirality representation Communications Chemistry |
| title | fragSMILES as a chemical string notation for advanced fragment and chirality representation |
| title_full | fragSMILES as a chemical string notation for advanced fragment and chirality representation |
| title_fullStr | fragSMILES as a chemical string notation for advanced fragment and chirality representation |
| title_full_unstemmed | fragSMILES as a chemical string notation for advanced fragment and chirality representation |
| title_short | fragSMILES as a chemical string notation for advanced fragment and chirality representation |
| title_sort | fragsmiles as a chemical string notation for advanced fragment and chirality representation |
| url | https://doi.org/10.1038/s42004-025-01423-3 |
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