f27125d78fa4dbf827487e67efd0a1b9 pmc_9966382.pdf b0d8f2a44e9568dd5fe839ba13ae377ca29ddfc3 pmc_9966382.pdf f24d4a7d5dc538c478191a1bd10ed718d5ff3336fd2c24f12adc2f0b9655f355 pmc_9966382.pdf Title: Rational Design of Hydrogels for Cationic Antimicrobial Peptide Delivery: A Molecular Modeling Approach Subject: In light of the growing bacterial resistance to antibiotics and in the absence of the development of new antimicrobial agents, numerous antimicrobial delivery systems over the past decades have been developed with the aim to provide new alternatives to the antimicrobial treatment of infections. However, there are few studies that focus on the development of a rational design that is accurate based on a set of theoretical-computational methods that permit the prediction and the understanding of hydrogels regarding their interaction with cationic antimicrobial peptides (cAMPs) as potential sustained and localized delivery nanoplatforms of cAMP. To this aim, we employed docking and Molecular Dynamics simulations (MDs) that allowed us to propose a rational selection of hydrogel candidates based on the propensity to form intermolecular interactions with two types of cAMPs (MP-L and NCP-3a). For the design of the hydrogels, specific building blocks were considered, named monomers (MN), co-monomers (CM), and cross-linkers (CL). These building blocks were ranked by considering the interaction with two peptides (MP-L and NCP-3a) as receptors. The better proposed hydrogel candidates were composed of MN3-CM7-CL1 and MN4-CM5-CL1 termed HG1 and HG2, respectively. The results obtained by MDs show that the biggest differences between the hydrogels are in the CM, where HG2 has two carboxylic acids that allow the forming of greater amounts of hydrogen bonds (HBs) and salt bridges (SBs) with both cAMPs. Therefore, using theoretical-computational methods allowed for the obtaining of the best virtual hydrogel candidates according to affinity with the specific cAMP. In conclusion, this study showed that HG2 is the better candidate for future in vitro or in vivo experiments due to its possible capacity as a depot system and its potential sustained and localized delivery system of cAMP. Keywords: cationic antimicrobial peptides; hydrogels; molecular docking; molecular dynamics simulations; virtual-screening; antibiotic resistance Author: Alfredo Pereira, Elizabeth Valdés-Muñoz, Adolfo Marican, Gustavo Cabrera-Barjas, Sekar Vijayakumar, Oscar Valdés, Diana Rafael, Fernanda Andrade, Paulina Abaca, Daniel Bustos and Esteban F. 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Building Blocks Selection Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Analysis of the Affinity between Hydrogel Building Blocks and cAMPs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Ensemble and Simulations of Hydrogel-cAMP Complexes Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Results and Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Ranking of Building Blocks by Molecular Docking Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Molecular Dynamics Simulations Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Info: Title: Rational Design of Hydrogels for Cationic Antimicrobial Peptide Delivery: A Molecular Modeling Approach Author: Alfredo Pereira, Elizabeth Valdés-Muñoz, Adolfo Marican, Gustavo Cabrera-Barjas, Sekar Vijayakumar, Oscar Valdés, Diana Rafael, Fernanda Andrade, Paulina Abaca, Daniel Bustos and Esteban F. Durán-Lara Subject: In light of the growing bacterial resistance to antibiotics and in the absence of the development of new antimicrobial agents, numerous antimicrobial delivery systems over the past decades have been developed with the aim to provide new alternatives to the antimicrobial treatment of infections. However, there are few studies that focus on the development of a rational design that is accurate based on a set of theoretical-computational methods that permit the prediction and the understanding of hydrogels regarding their interaction with cationic antimicrobial peptides (cAMPs) as potential sustained and localized delivery nanoplatforms of cAMP. To this aim, we employed docking and Molecular Dynamics simulations (MDs) that allowed us to propose a rational selection of hydrogel candidates based on the propensity to form intermolecular interactions with two types of cAMPs (MP-L and NCP-3a). For the design of the hydrogels, specific building blocks were considered, named monomers (MN), co-monomers (CM), and cross-linkers (CL). These building blocks were ranked by considering the interaction with two peptides (MP-L and NCP-3a) as receptors. The better proposed hydrogel candidates were composed of MN3-CM7-CL1 and MN4-CM5-CL1 termed HG1 and HG2, respectively. The results obtained by MDs show that the biggest differences between the hydrogels are in the CM, where HG2 has two carboxylic acids that allow the forming of greater amounts of hydrogen bonds (HBs) and salt bridges (SBs) with both cAMPs. Therefore, using theoretical-computational methods allowed for the obtaining of the best virtual hydrogel candidates according to affinity with the specific cAMP. In conclusion, this study showed that HG2 is the better candidate for future in vitro or in vivo experiments due to its possible capacity as a depot system and its potential sustained and localized delivery system of cAMP. Keywords: cationic antimicrobial peptides; hydrogels; molecular docking; molecular dynamics simulations; virtual-screening; antibiotic resistance Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Feb 09 10:38:13 CET 2023 ModDate: Thu Feb 16 04:18:29 CET 2023 ID: 0x92e105f7039e2dd8fe4b860b4f52cd05, 0x92e105f7039e2dd8fe4b860b4f52cd05 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: GXETXL+URWPalladioL-BoldItal FontSubset: true FirstChar: 46 LastChar: 117 FontDescriptor: FontName: GXETXL+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: FUORSM+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 241 FontDescriptor: FontName: FUORSM+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: FPQOSI+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 246 FontDescriptor: FontName: 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