دورية أكاديمية
أعرض في EDS

DeLA-DrugSelf: Empowering multi-objective de novo design through SELFIES molecular representation.

التفاصيل البيبلوغرافية
العنوان: DeLA-DrugSelf: Empowering multi-objective de novo design through SELFIES molecular representation.
المؤلفون: Alberga D; CNR - Institute of Crystallography, Via Amendola 122/o, 70126, Bari, Italy., Lamanna G; CNR - Institute of Crystallography, Via Amendola 122/o, 70126, Bari, Italy., Graziano G; Department of Pharmacy - Pharmaceutical Sciences, University of Bari 'Aldo Moro', via E. Orabona, 4, I-70125, Bari, Italy., Delre P; CNR - Institute of Crystallography, Via Amendola 122/o, 70126, Bari, Italy., Lomuscio MC; CNR - Institute of Crystallography, Via Amendola 122/o, 70126, Bari, Italy., Corriero N; CNR - Institute of Crystallography, Via Amendola 122/o, 70126, Bari, Italy., Ligresti A; CNR - Institute of Biomolecular Chemistry, Via Campi Flegrei 34, 80078, Pozzuoli, Italy., Siliqi D; CNR - Institute of Crystallography, Via Amendola 122/o, 70126, Bari, Italy., Saviano M; CNR - Institute of Crystallography, Via Vivaldi 43, 81100, Caserta, Italy., Contino M; Department of Pharmacy - Pharmaceutical Sciences, University of Bari 'Aldo Moro', via E. Orabona, 4, I-70125, Bari, Italy., Stefanachi A; Department of Pharmacy - Pharmaceutical Sciences, University of Bari 'Aldo Moro', via E. Orabona, 4, I-70125, Bari, Italy., Mangiatordi GF; CNR - Institute of Crystallography, Via Amendola 122/o, 70126, Bari, Italy. Electronic address: giuseppefelice.mangiatordi@cnr.it.
المصدر: Computers in biology and medicine [Comput Biol Med] 2024 Jun; Vol. 175, pp. 108486. Date of Electronic Publication: 2024 Apr 16.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 1250250 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0534 (Electronic) Linking ISSN: 00104825 NLM ISO Abbreviation: Comput Biol Med Subsets: MEDLINE
أسماء مطبوعة: Publication: New York : Elsevier
Original Publication: New York, Pergamon Press.
مواضيع طبية MeSH: Software* , Algorithms*, Drug Design ; Humans
مستخلص: In this paper, we introduce DeLA-DrugSelf, an upgraded version of DeLA-Drug [J. Chem. Inf. Model. 62 (2022) 1411-1424], which incorporates essential advancements for automated multi-objective de novo design. Unlike its predecessor, which relies on SMILES notation for molecular representation, DeLA-DrugSelf employs a novel and robust molecular representation string named SELFIES (SELF-referencing Embedded String). The generation process in DeLA-DrugSelf not only involves substitutions to the initial string representing the starting query molecule but also incorporates insertions and deletions. This enhancement makes DeLA-DrugSelf significantly more adept at executing data-driven scaffold decoration and lead optimization strategies. Remarkably, DeLA-DrugSelf explicitly addresses the SELFIES-related collapse issue, considering only collapse-free compounds during generation. These compounds undergo a rigorous quality metrics evaluation, highlighting substantial advancements in terms of drug-likeness, uniqueness, and novelty compared to the molecules generated by the previous version of the algorithm. To evaluate the potential of DeLA-DrugSelf as a mutational operator within a genetic algorithm framework for multi-objective optimization, we employed a fitness function based on Pareto dominance. Our objectives focused on target-oriented properties aimed at optimizing known cannabinoid receptor 2 (CB2R) ligands. The results obtained indicate that DeLA-DrugSelf, available as a user-friendly web platform (https://www.ba.ic.cnr.it/softwareic/delaself/), can effectively contribute to the data-driven optimization of starting bioactive molecules based on user-defined parameters.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Domenico Alberga reports financial support was provided by European Union. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
تواريخ الأحداث: Date Created: 20240423 Date Completed: 20240513 Latest Revision: 20240513
رمز التحديث: 20240514
DOI: 10.1016/j.compbiomed.2024.108486
PMID: 38653065
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-0534
DOI:10.1016/j.compbiomed.2024.108486