Discovery of novel MDR-mycobacterium tuberculosis inhibitor by new FRIGATE computational screen

Christoph Scheich, Zoltán Szabadka, B. Vértessy, Vera Pütter, Vince Grolmusz, Markus Schade

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

With 1.6 million casualties annually and 2 billion people being infected, tuberculosis is still one of the most pressing healthcare challenges. Here we report on the new computational docking algorithm FRIGATE which unites continuous local optimization techniques (conjugate gradient method) with an inherently discrete computational approach in forcefield computation, resulting in equal or better scoring accuracies than several benchmark docking programs. By utilizing FRIGATE for a virtual screen of the ZINC library against the Mycobacterium tuberculosis (Mtb) enzyme antigen 85C, we identified novel small molecule inhibitors of multiple drug-resistant Mtb, which bind in vitro to the catalytic site of antigen 85C.

Original languageEnglish
Article numbere28428
JournalPLoS One
Volume6
Issue number12
DOIs
Publication statusPublished - Dec 2 2011

Fingerprint

Benchmarking
Multidrug-Resistant Tuberculosis
Mycobacterium tuberculosis
Libraries
Catalytic Domain
Tuberculosis
antigens
Delivery of Health Care
Antigens
Conjugate gradient method
pressing
Enzymes
tuberculosis
active sites
health services
drugs
Molecules
enzymes
methodology
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Discovery of novel MDR-mycobacterium tuberculosis inhibitor by new FRIGATE computational screen. / Scheich, Christoph; Szabadka, Zoltán; Vértessy, B.; Pütter, Vera; Grolmusz, Vince; Schade, Markus.

In: PLoS One, Vol. 6, No. 12, e28428, 02.12.2011.

Research output: Contribution to journalArticle

Scheich, Christoph ; Szabadka, Zoltán ; Vértessy, B. ; Pütter, Vera ; Grolmusz, Vince ; Schade, Markus. / Discovery of novel MDR-mycobacterium tuberculosis inhibitor by new FRIGATE computational screen. In: PLoS One. 2011 ; Vol. 6, No. 12.
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