Screening of novel and selective inhibitors for neuronal nitric oxide synthase (nNOS) via structure-based drug design techniques

dc.contributor.advisorYelekci, Kemalen_US
dc.contributor.authorboumezber, sarah
dc.contributor.authorYelekçi, Kemal
dc.date2022-01
dc.date.accessioned2023-07-25T07:53:16Z
dc.date.available2023-07-25T07:53:16Z
dc.date.issued2022
dc.departmentEnstitüler, Lisansüstü Eğitim Enstitüsü, Biyoinformatik ve Genetik Ana Bilim Dalıen_US
dc.description.abstractThe overproduction of nitric oxide (NO) by neuronal nitric oxide synthase (nNOS) is the main cause of several neurodegenerative diseases such as Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and Multiple Sclerosis (MS). NO is produced in many cell types by three isoforms of NOS (nNOS, iNOS, and eNOS) and has various biological functions, generally, for its significant reactivity with proteins. NOS isoforms share a high sequence and structure similarity, specifically in the active site, which makes the development and design of nNOS inhibitors extremely challenging; mainly, no-selective inhibitors can affect iNOS and eNOS physiological roles. To date, there is no selective inhibitor against nNOS in the market with desirable ADMET (absorption, distribution, metabolism, elimination, and toxicity) properties, and pass the blood-brain barrier (BBB). With improvement of computational drug design techniques and accessibility of the X-ray crystal structures, development of novel drugs became less expensive and faster. Our research benefited from the structure-based drug design approaches to investigate proficient and selective inhibitors against nNOS. After structure-based virtual screening, the selective top-ranked compounds were filtered according to the ADMET prediction; then, the candidates with a high affinity with a suitable ADMET profile were subject to 100 ns molecular dynamics (MD) simulations. The stability through the 100 ns run has been evident for some nominated inhibitors, which are valuable lead compounds that can be optimized to reach the greatest physicochemical properties in addition to the selectivity.en_US
dc.identifier.pmid35322764en_US
dc.identifier.scopus2-s2.0-85127140851en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12469/4362
dc.identifier.wosWOS:000772288000001en_US
dc.identifier.yoktezid726268en_US
dc.language.isoenen_US
dc.publisherKadir Has Üniversitesien_US
dc.relation.publicationcategoryTezen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectNitric Oxideen_US
dc.subjectStructure-Based Drug Designen_US
dc.subjectNeuronal Nitric Oxide Synthaseen_US
dc.subjectNeurodegenerative Diseasesen_US
dc.subjectADMET Propertiesen_US
dc.subjectSelective nNOS Inhibitorsen_US
dc.subjectMolecular Dynamics Simulationen_US
dc.titleScreening of novel and selective inhibitors for neuronal nitric oxide synthase (nNOS) via structure-based drug design techniquesen_US
dc.typeDoctoral Thesisen_US
dspace.entity.typePublication
relation.isAuthorOfPublication9407938e-3d31-453b-9199-aaa8280a66c5
relation.isAuthorOfPublication.latestForDiscovery9407938e-3d31-453b-9199-aaa8280a66c5

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Screening of Novel and Selective Inhibitors for Neuronal Nitric Oxide Dynthase (nNOS) Via Structure-Based Drug Design Techniques

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