Targeting plague virulence factors: a combined machine learning method and multiple conformational virtual screening for the discovery of Yersinia protein kinase A inhibitors.
Yersinia spp. is currently an antibiotic resistance concern and a re-emerging disease. The essential virulence factor Yersinia protein kinase A (YpkA) contains a Ser/Thr kinase domain whose activity modulates pathogenicity. Here, we present an approach integrating a machine learning method, homology modeling, and multiple conformational high-throughput docking for the discovery of YpkA inhibitors. These first reported inhibitors of YpkA may facilitate studies of the pathogenic mechanism of YpkA and serve as a starting point for development of anti-plague drugs.
Hu
Xin
X
Laboratory of Structural Microbiology, The Rockefeller University, New York, New York 10021, USA.
Prehna
Gerd
G
Stebbins
C Erec
CE
D000595:Amino Acid Sequence; D000880:Anthraquinones / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001185:Artificial Intelligence; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010930:Plague / Q000382:microbiology*; D011493:Protein Kinase C / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000737:chemistry*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D017386:Sequence Homology, Amino Acid; D037521:Virulence Factors / Q000037:antagonists & inhibitors / Q000737:chemistry*; D015007:Yersinia / Q000201:enzymology*
D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D037521:Virulence Factors; C079893:ypkA protein, Yersinia; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases