Ligand-Based Pharmacophore Modeling Using Novel 3D Pharmacophore Signatures

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F18%3A73593947" target="_blank" >RIV/61989592:15110/18:73593947 - isvavai.cz</a>

Výsledek na webu

<a href="https://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=GeneralSearch&qid=13&SID=E49vWjmiOCcIVNcWJeQ&page=1&doc=1" target="_blank" >https://apps.webofknowledge.com/full_record.do?product=WOS&search_mode=GeneralSearch&qid=13&SID=E49vWjmiOCcIVNcWJeQ&page=1&doc=1</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/molecules23123094" target="_blank" >10.3390/molecules23123094</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Ligand-Based Pharmacophore Modeling Using Novel 3D Pharmacophore Signatures

Popis výsledku v původním jazyce

Pharmacophore modeling is a widely used strategy for finding new hit molecules. Since not all protein targets have available 3D structures, ligand-based approaches are still useful. Currently, there are just a few free ligand-based pharmacophore modeling tools, and these have a lot of restrictions, e.g., using a template molecule for alignment. We developed a new approach to 3D pharmacophore representation and matching which does not require pharmacophore alignment. This representation can be used to quickly find identical pharmacophores in a given set. Based on this representation, a 3D pharmacophore ligand-based modeling approach to search for pharmacophores which preferably match active compounds and do not match inactive ones was developed. The approach searches for 3D pharmacophore models starting from 2D structures of available active and inactive compounds. The implemented approach was successfully applied for several retrospective studies. The results were compared to a 2D similarity search, demonstrating some of the advantages of the developed 3D pharmacophore models. Also, the generated 3D pharmacophore models were able to match the 3D poses of known ligands from their protein-ligand complexes, confirming the validity of the models. The developed approach is available as an open-source software tool: http://www.qsar4u.com/pages/pmapper.php and https://github.com/meddwl/psearch.

Název v anglickém jazyce

Ligand-Based Pharmacophore Modeling Using Novel 3D Pharmacophore Signatures

Popis výsledku anglicky

Pharmacophore modeling is a widely used strategy for finding new hit molecules. Since not all protein targets have available 3D structures, ligand-based approaches are still useful. Currently, there are just a few free ligand-based pharmacophore modeling tools, and these have a lot of restrictions, e.g., using a template molecule for alignment. We developed a new approach to 3D pharmacophore representation and matching which does not require pharmacophore alignment. This representation can be used to quickly find identical pharmacophores in a given set. Based on this representation, a 3D pharmacophore ligand-based modeling approach to search for pharmacophores which preferably match active compounds and do not match inactive ones was developed. The approach searches for 3D pharmacophore models starting from 2D structures of available active and inactive compounds. The implemented approach was successfully applied for several retrospective studies. The results were compared to a 2D similarity search, demonstrating some of the advantages of the developed 3D pharmacophore models. Also, the generated 3D pharmacophore models were able to match the 3D poses of known ligands from their protein-ligand complexes, confirming the validity of the models. The developed approach is available as an open-source software tool: http://www.qsar4u.com/pages/pmapper.php and https://github.com/meddwl/psearch.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LTARF18013" target="_blank" >LTARF18013: Zvýšení úspěšnosti primárního skríningu biologicky aktivních látek pomocí výpočetních modelů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2018

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

MOLECULES

ISSN

1420-3049

e-ISSN

—

Svazek periodika

23

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

14

Strana od-do

"nestránkováno"

Kód UT WoS článku

000454523000044

EID výsledku v databázi Scopus

2-s2.0-85057470675