In silico QSAR and molecular docking simulation of some novel aryl sulfonamide derivatives as inhibitors of H5N1 influenza A virus subtype
Mustapha Abdullahi, Gideon Adamu Shallangwa, Adamu Uzairu
Abstract
Abstract Background This research provides a comprehensive analysis of QSAR modeling performed on 25 aryl sulfonamide derivatives to predict their effective concentration (EC 50 ) against H5N1 influenza A virus by using some numerical information derived from structural and chemical features (descriptors) of the compounds to generate a statistically significant model. Subsequently, the molecular docking simulations were done so as to determine the binding modes of some potent ligands in the dataset with the M2 proton channel protein of the H5N1 influenza A virus as the target. Results In building the QSAR model, the genetic algorithm task was employed in the variable selection of the descriptors which are used to form the multi-linear regression equation. The model with descriptors, RDF100m, nO, and RDF45p, showed satisfactory internal and external validation parameters ( R 2 train = 0.72963, R 2 adjusted = 0.67169, Q 2 cv = 0.598, $$ {R}_{\mathrm{pred}}^2= $$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msubsup><mml:mi>R</mml:mi><mml:mtext>pred</mml:mtext><mml:mn>2</mml:mn></mml:msubsup><mml:mo>=</mml:mo></mml:math> 0.67295, R 2 test = 0.6860) which passed the model criteria of acceptability. Docking simulation results of the more potent compounds (ligands 2, 3, and 8) revealed the formation of hydrophobic and hydrogen bonds with the binding pockets of M2 protein of influenza A virus. Conclusion The results in this study can help to advance the research in designing (in silico design) and synthesis of more potent aryl sulfonamides derivatives against H5N1 influenza virus.