Repository logo
 
Publication

Binding free energy calculations using MMPB/GBSA approaches for PAMAM-G4-drug complexes at neutral, basic and acid pH conditions

2017Journal article Restricted access
Simple item page
dc.contributor.authorMartínez-Muñoz, Alberto
dc.contributor.authorBello, Martiniano
dc.contributor.authorRomero-Castro, Aurelio
dc.contributor.authorRodríguez-Fonseca, Rolando Alberto
dc.contributor.authorRodrigues, João
dc.contributor.authorSánchez-Espinosa, Víctor Armando
dc.contributor.authorCorrea-Basurto, José
dc.date.accessioned2019-06-25T14:01:36Z
dc.date.available2019-06-25T14:01:36Z
dc.date.issued2017
dc.description.abstractDendrimers are synthetic macromolecules with a highly-branched structure and high concentration of surface groups. Among dendrimers, Poly(amidoamine) (PAMAM) has received substantial attention as a novel drug carrier and delivery system. Depending on the generation and type of terminal groups, dendrimer toxicity could change and include cytotoxicity. Although PAMAM is water soluble, molecular modeling of the dendrimer-drug complex is considered challenging for exploring the conformational mobility of dendrimers and atomic specific interactions during the dendrimer-drug association. However, conventional protocols for predicting binding affinities have been designed for small protein molecules or protein-protein complexes that can be applied to study the dendrimer-drug association. In this work, we performed docking calculations for a set of 94 previously reported compounds on PAMAM of fourth generation (G4-PAMAM) to select six compounds, cromoglicic acid (CRO) - a mast cell stabilizer, Fusidic acid (FUS) - a bacteriostatic antibiotic, and Methotrexate (MTX) - a chemotherapy agent and immune system suppressant, which have the highest affinities for G4-PAMAM, and Lidocaine (LDC) - used to numb tissue in a specific area and for ventricular tachycardia treatment, Metoprolol (MET) - a β1 receptor blocker, and Pindolol (PIN) - a β blocker, which have the lowest affinities for the G4-PAMAM dendrimer, to perform MD simulations combined with the molecular mechanics generalized/Poisson-Boltzmann surface area MMGBSA/MMPBSA approach to investigate the interactions of generating 4 charge-neutral, charge-basic and charge-acid G4-PAMAM dendrimers. In addition, to validate these theoretical G4-PAMAM-drug complexes, the complexes were experimentally conjugated to determine their stability in aqueous solubility studies immediately and over one year. Our results show that among the different commercial drugs, both charged and neutral PAMAM have the most favorable binding free energies for CRO, MTX, and FUS, which appears to be due to a complex counterbalance of electrostatics and van der Waals interactions. These theoretical and aqueous solubility studies supported the high affinity of methotrexate for the G4-PAMAM-drug due to its carboxyl and aryl moieties that favor its accommodation by noncovalent interactions.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.jmgm.2017.07.017pt_PT
dc.identifier.issn1093-3263
dc.identifier.urihttp://hdl.handle.net/10400.13/2431
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationMadeira Chemistry Research Centre
dc.subjectG4-PAMAM dendrimerpt_PT
dc.subjectHydrophobic and Hydrophilic Interactionspt_PT
dc.subjectDrugspt_PT
dc.subjectDocking molecular dynamics simulationspt_PT
dc.subjectHPLCpt_PT
dc.subject.pt_PT
dc.subjectFaculdade de Ciências Exatas e da Engenhariapt_PT
dc.titleBinding free energy calculations using MMPB/GBSA approaches for PAMAM-G4-drug complexes at neutral, basic and acid pH conditionspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMadeira Chemistry Research Centre
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FQUI%2F00674%2F2013/PT
oaire.citation.endPage341pt_PT
oaire.citation.startPage330pt_PT
oaire.citation.titleJournal of Molecular Graphics and Modellingpt_PT
oaire.citation.volume76pt_PT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameROMERO-CASTRO
person.familyNameRodrigues
person.givenNameAURELIO
person.givenNameJoão
person.identifier.ciencia-idA81C-620E-DD6A
person.identifier.orcid0000-0001-7135-7339
person.identifier.orcid0000-0003-4552-1953
person.identifier.ridB-6816-2008
person.identifier.scopus-author-id37067913200
person.identifier.scopus-author-id9233278800
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationfa87792f-ca3b-4e85-8c58-4e27b0eed4cc
relation.isAuthorOfPublication53031fca-b2e7-4ce4-bda9-61e486da4547
relation.isAuthorOfPublication.latestForDiscovery53031fca-b2e7-4ce4-bda9-61e486da4547
relation.isProjectOfPublicationfd9571e0-489f-4866-8f87-99dadd8a09d5
relation.isProjectOfPublication.latestForDiscoveryfd9571e0-489f-4866-8f87-99dadd8a09d5

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Binding Free Energy Calculations Using MMPB GBSA Approaches for PAMAM-G4-Drug Complexes at Neutral.pdf
Size:
3.15 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Artigos em revistas internacionais