Combining CBP Pharmacophore Construction and Molecular Docking to Search for Potential Competitive Inhibitors of Chitin Deacetylase

Abstract

Chitin deacetylase (CDA) is a key enzyme for plant pathogens to evade host defense recognition. However, in the study of CDA inhibitors, only chitin deacetylase from colletotrichum lindemuthianum (ClCDA) was found to participate in the reverse hydrolysis reaction in sodium acetate to acetylate free amino sugar residues into N-acetylated forms. Based on this, we selected 10,632 small molecules from the DrugBank database for computer virtual screening to find new potential CDA inhibitors. First, we use the CBP model with ROC = 0.800 to coarsely screen small molecules. Then we use the LibDock and CDOCKER programs in Discovery Studio 2016 (DS 2016) to dock the best-matched small molecules to identify interactions with key residues on the active site of ClCDA. Finally, we found two potential compounds with good adaptability, high docking score and important interactions with protein active sites. And we confirm that their structures are stable and have multiple non-bonding interactions with important amino acid sites such as ASP50, TYR145, HIS206 and ZN1255 by MD simulations. Therefore, we conclude that the selected compounds are likely to be new inhibitors of CDA. In this research could provide a valuable resource and guidance for CDA-related inhibitors development.

Discovery of Chitin Deacetylase Inhibitors through Structure-Based Virtual Screening and Biological Assays

“…SBVS has opened up new avenues for enzyme inhibitor designing. However, to our knowledge, there has only been one report on Chitin deacetylase (CDA) inhibitor screening so far [ 20 ].…”