Structure-Based Virtual Screening: New Methods and Applications in Infectious Diseases

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Sökning: WFRF:(Karlén Anders Professor) > Structure-Based Vir...

Jacobsson, Micael,1975-Uppsala universitet,Avdelningen för organisk farmaceutisk kemi (författare)

Structure-Based Virtual Screening : New Methods and Applications in Infectious Diseases

BokEngelska2008

Förlag, utgivningsår, omfång ...

Uppsala :Acta Universitatis Upsaliensis,2008
86 s.
electronicrdacarrier

Nummerbeteckningar

LIBRIS-ID:oai:DiVA.org:uu-9302
ISBN:9789155472979
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9302URI

Kompletterande språkuppgifter

Språk:engelska
Sammanfattning på:engelska

Ingår i deldatabas

SwePubSwePub

Klassifikation

Ämneskategori:vet swepub-contenttype
Ämneskategori:dok swepub-publicationtype

Serie

Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy,1651-6192 ;82

Anmärkningar

A drug discovery project typically starts with a pharmacological hypothesis: that the modulation of a specific molecular biological mechanism would be beneficial in the treatment of the targeted disease. In a small-molecule project, the next step is to identify hits, i.e. molecules that can effect this modulation. These hits are subsequently expanded into hit series, which are optimised with respect to pharmacodynamic and pharmacokinetic properties, through medicinal chemistry. Finally, a drug candidate is clinically developed into a new drug. This thesis concerns the use of structure-based virtual screening in the hit identification phase of drug discovery.Structure-based virtual screening involves using the known 3D structure of a target protein to predict binders, through the process of docking and scoring. Docking is the prediction of potential binding poses, and scoring is the prediction of the free energy of binding from those poses. Two new methodologies, based on post-processing of scoring results, were developed and evaluated using model systems. Both methods significantly increased the enrichment of true positives. Furthermore, correlation was observed between scores and simple molecular properties, and identified as a source of false positives in structure-based virtual screening.Two target proteins, Mycobacterium tuberculosis ribose-5-phosphate isomerase, a potential drug target in tuberculosis, and Plasmodium falciparum spermidine synthase, a potential drug target in malaria, were subjected to docking and virtual screening. Docking of substrates and products of ribose-5-phosphate isomerase led to hypotheses on the role of individual residues in the active site. Additionally, virtual screening was used to predict 48 potential inhibitors, but none was confirmed as an inhibitor or binder to the target enzyme. For spermidine synthase, structure-based virtual screening was used to predict 32 potential active-site binders. Seven of these were confirmed to bind in the active site.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Läkemedelskemi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medicinal Chemistry hsv//eng
: drug discovery
docking
scoring
virtual screening
malaria
tuberculosis
Pharmaceutical chemistry
Läkemedelskemi

Biuppslag (personer, institutioner, konferenser, titlar ...)

Karlén, Anders,ProfessorUppsala universitet,Avdelningen för organisk farmaceutisk kemi (preses)
Kihlén, Mats (preses)
Poso, Antti,ProfessorDepartment of Pharmaceutical Chemistry, University of Kuopio (opponent)
Uppsala universitetAvdelningen för organisk farmaceutisk kemi (creator_code:org_t)

Internetlänk

Hitta via bibliotek

Structure-Based Virtual Screening New Methods and Applications in Infectious Dis... (Sök publikationen i LIBRIS)

Till lärosätets databas

Hitta mer i SwePub

Av författaren/redakt...: Jacobsson, Micae ...; Karlén, Anders, ...; Kihlén, Mats; Poso, Antti, Pro ...

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Läkemedelskemi

Delar i serien: Digital Comprehe ...

Av lärosätet: Uppsala universitet

Sök utanför SwePub

Sök vidare i:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se