dc.contributor
Universitat Jaume I. Escola de Doctorat
cat
dc.contributor.author
Movilla Núñez, Santiago
dc.date.accessioned
2023-02-07T15:22:41Z
dc.date.available
2023-02-07T15:22:41Z
dc.date.issued
2023-01-27
dc.identifier.uri
http://hdl.handle.net/10803/687601
dc.description
Doctorat internacional
ca
dc.description.abstract
Since its identification in 1901, by the German psychiatrist Alois Alzheimer, Alzheimer's disease has emerged as one of the greatest challenges in pharmaceutical research. In 2019, the cysteine protease RgpB was identified as a possible new pharmacological target for the development of neuroprotective treatments using small drugs-like molecules. This thesis represents an effort to shed light on atomic-level details of the mechanisms by which the RgpB works and the processes of its inhibition by small-molecule drug candidates. For this purpose, a comprehensive computational study combining methods based on classical molecular dynamics and hybrid quantum mechanics/molecular mechanics molecular dynamics was carried out. These methods were employed to obtain reaction free energies and binding free energies. This allows us to elucidate the mechanism by which the proteolysis reaction proceeds on RgpB, to characterize non-covalent interaction profiles between putative inhibitors and RgpB and to unravel the covalent binding mechanisms of such irreversible inhibitors.
ca
dc.format.extent
293 p.
ca
dc.publisher
Universitat Jaume I
dc.rights.license
L'accés als continguts d'aquesta tesi queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons: https://creativecommons.org/licenses/by-nc/4.0/deed.es
ca
dc.rights.uri
https://creativecommons.org/licenses/by-nc/4.0/deed.es
*
dc.source
TDX (Tesis Doctorals en Xarxa)
dc.subject
Molecular Modelling
ca
dc.subject
Computational Chemistry
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dc.subject.other
Ciències
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dc.title
Computational Study on the Reactivity and Inhibition of Arginine Gingipain B, a Potential Target for the Treatment of Alzheimer's Disease
ca
dc.type
info:eu-repo/semantics/doctoralThesis
dc.type
info:eu-repo/semantics/publishedVersion
dc.contributor.director
Moliner, Vicent
dc.contributor.director
Roca Moliner, María Teresa
dc.contributor.tutor
Moliner, Vicent
dc.rights.accessLevel
info:eu-repo/semantics/openAccess
dc.identifier.doi
http://dx.doi.org/10.6035/14122.2023.808904
ca
dc.description.degree
Programa de Doctorat en Química Teòrica i Modelització Computacional