Structural Requirements of N-alpha-Mercaptoacetyl Dipeptide (NAMdP) Inhibitors of Pseudomonas Aeruginosa Virulence Factor LasB: 3D-QSAR, Molecular Docking, and Interaction Fingerprint Studies

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dc.contributor.authorVelázquez-Libera, José Luis
dc.contributor.authorMurillo-López, Juliana Andrea
dc.contributor.authorde la Torre, Alexander F.
dc.contributor.authorCaballero, Julio
dc.date.accessioned2021-09-02T16:09:59Z
dc.date.available2021-09-02T16:09:59Z
dc.date.issued2019-12
dc.descriptionIndexación: Scopus.es
dc.description.abstractThe zinc metallopeptidase Pseudomonas elastase (LasB) is a virulence factor of Pseudomonas aeruginosa (P. aeruginosa), a pathogenic bacterium that can cause nosocomial infections. The present study relates the structural analysis of 118 N-alpha-mercaptoacetyl dipeptides (NAMdPs) as LasB inhibitors. Field-based 3D-QSAR and molecular docking methods were employed to describe the essential interactions between NAMdPs and LasB binding sites, and the chemical features that determine their differential activities. We report a predictive 3D-QSAR model that was developed according to the internal and external validation tests. The best model, including steric, electrostatic, hydrogen bond donor, hydrogen bond acceptor, and hydrophobic fields, was found to depict a three-dimensional map with the local positive and negative effects of these chemotypes on the LasB inhibitory activities. Furthermore, molecular docking experiments yielded bioactive conformations of NAMdPs inside the LasB binding site. The series of NAMdPs adopted a similar orientation with respect to phosphoramidon within the LasB binding site (crystallographic reference), where the backbone atoms of NAMdPs are hydrogen-bonded to the LasB residues N112, A113, and R198, similarly to phosphoramidon. Our study also included a deep description of the residues involved in the protein–ligand interaction patterns for the whole set of NAMdPs, through the use of interaction fingerprints (IFPs). © 2019 by the authors. Licensee MDPI, Basel, Switzerland.es
dc.description.urihttps://www.mdpi.com/1422-0067/20/24/6133
dc.identifier.citationInternational Journal of Molecular Sciences Volume 20, Issue 242 December 2019 Article number 6133es
dc.identifier.doi10.3390/ijms20246133
dc.identifier.issn1661-6596
dc.identifier.urihttp://repositorio.unab.cl/xmlui/handle/ria/20095
dc.language.isoenes
dc.publisherMDPI AGes
dc.rights.licenseAtribución 4.0 Internacional (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subject3D-QSARes
dc.subjectDocking; Interaction fingerprintses
dc.subjectN-alpha-mercaptoacetyl dipeptideses
dc.subjectPseudomonas aeruginosa elastasees
dc.titleStructural Requirements of N-alpha-Mercaptoacetyl Dipeptide (NAMdP) Inhibitors of Pseudomonas Aeruginosa Virulence Factor LasB: 3D-QSAR, Molecular Docking, and Interaction Fingerprint Studieses
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