Discovery of Novel MDR-Mycobacterium tuberculosis Inhibitor by New FRIGATE Computational Screen

被引：13

作者：

Scheich, Christoph ^{[1
]}

Szabadka, Zoltan ^{[2
,4
]}

Vertessy, Beata ^{[3
,5
]}

Puetter, Vera ^{[1
]}

Grolmusz, Vince ^{[2
]}

Schade, Markus ^{[1
]}

机构：

[1] Combinat Biopharm AG, Berlin, Germany

[2] Eotvos Lorand Univ, Dept Comp Sci, Budapest, Hungary

[3] Hungarian Acad Sci, Inst Enzymol, Budapest, Hungary

[4] Uratim Ltd, Budapest, Hungary

[5] Univ Technol & Econ, Dept Appl Biotechnol, Budapest, Hungary

来源：

PLOS ONE | 2011年 / 6卷 / 12期

基金：

匈牙利科学研究基金会;

关键词：

ANTIGEN; 85C; DRUGS; DESIGN; BIOSYNTHESIS; ALGORITHM; MECHANISM; DOCKING; INDEXES; ENZYME;

D O I：

10.1371/journal.pone.0028428

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：9

共 38 条

[1] Ligand efficiency indices as guideposts for drug discovery [J].