Computational Study on the Reactivity and Inhibition of Arginine Gingipain B, a Potential Target for the Treatment of Alzheimer's Disease
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comunitat-uji-handle2:10234/29747
comunitat-uji-handle3:10234/162758
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TESISMetadades
Títol
Computational Study on the Reactivity and Inhibition of Arginine Gingipain B, a Potential Target for the Treatment of Alzheimer's DiseaseAutoria
Director/a
Moliner, Vicent; Roca Moliner, María TeresaPrograma de Doctorat
Programa de Doctorat en Química Teòrica i Modelització ComputacionalÒrgan responsable
Universitat Jaume I. Escola de DoctoratData de defensa
2023-01-27Descripció
Doctorat internacional
Editor
Universitat Jaume IParaules clau
Àrea de coneixement
Pàgines
293 p.Resum
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 ... [+]
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. [-]
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info:eu-repo/semantics/openAccess
info:eu-repo/semantics/openAccess