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Unraveling the Hemolytic Toxicity Tapestry of Peptides using Chemical Space Complex Networks.
Castillo-Mendieta, Kevin; Agüero-Chapin, Guillermin; Mora, José R; Pérez, Noel; Contreras-Torres, Ernesto; Valdes-Martini, José R; Martinez-Rios, Felix; Marrero-Ponce, Yovani.
Afiliação
  • Castillo-Mendieta K; School of Biological Sciences and Engineering, Yachay Tech University, Hda. San José s/n y Proyecto Yachay, Urcuquí, 100119, Ecuador.
  • Agüero-Chapin G; CIIMAR/CIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, Porto, 4450-208, Portugal.
  • Mora JR; Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, Porto, 4169-007, Portugal.
  • Pérez N; Universidad San Francisco de Quito (USFQ), Colegio de Ciencias e Ingenierías "El Politécnico", Diego de Robles y vía Interoceánica, Pichincha, Quito, 170157, Ecuador.
  • Contreras-Torres E; Universidad San Francisco de Quito (USFQ), Colegio de Ciencias e Ingenierías "El Politécnico", Diego de Robles y vía Interoceánica, Pichincha, Quito, 170157, Ecuador.
  • Valdes-Martini JR; Universidad San Francisco de Quito (USFQ), Grupo de Medicina Molecular y Traslacional (MeM&T), Colegio de Ciencias de la Salud (COCSA), Escuela de Medicina, Edificio de Especialidades Médicas and Instituto de Simulación Computacional (ISC-USFQ), Diego de Robles y vía Interoceánica, Pichincha, Qu
  • Martinez-Rios F; Undoso Consulting, Miami, FL, 33185, USA.
  • Marrero-Ponce Y; Facultad de Ingeniería, Universidad Panamericana, Augusto Rodin No. 498, Insurgentes Mixcoac, Benito Juárez, Ciudad de México, 03920, México.
Toxicol Sci ; 2024 Sep 10.
Article em En | MEDLINE | ID: mdl-39254655
ABSTRACT
Peptides have emerged as promising therapeutic agents. However, their potential is hindered by hemotoxicity. Understanding the hemotoxicity of peptides is crucial for developing safe and effective peptide-based therapeutics. Here, we employed chemical space complex networks (CSNs) to unravel the hemotoxicity tapestry of peptides. CSNs are powerful tools for visualizing and analyzing the relationships between peptides based on their physicochemical properties and structural features. We constructed CSNs from the StarPepDB database, encompassing 2004 hemolytic peptides, and explored the impact of seven different (dis)similarity measures on network topology and cluster (communities) distribution. Our findings revealed that each CSN extracts orthogonal information, enhancing the motif discovery and enrichment process. We identified 12 consensus hemolytic motifs, whose amino acid composition unveiled a high abundance of lysine, leucine, and valine residues, while aspartic acid, methionine, histidine, asparagine and glutamine were depleted. Additionally, physicochemical properties were used to characterize clusters/communities of hemolytic peptides. To predict hemolytic activity directly from peptide sequences, we constructed multi-query similarity searching models (MQSSMs), which outperformed cutting-edge machine learning (ML)-based models, demonstrating robust hemotoxicity prediction capabilities. Overall, this novel in silico approach uses complex network science as its central strategy to develop robust model classifiers, to characterize the chemical space and to discover new motifs from hemolytic peptides. This will help to enhance the design/selection of peptides with potential therapeutic activity and low toxicity.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Toxicol Sci Assunto da revista: TOXICOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Equador País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Toxicol Sci Assunto da revista: TOXICOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Equador País de publicação: Estados Unidos