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6-Ethoxy-4- N-(2-morpholin-4-ylethyl) -2-N-propan-2-yl-1,3, 5-triazine-2, 4-diamine endows herbicidal activity against Phalaris minor a weed of wheat crop field: An in -silico and experimental approaches of herbicide discovery

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Abstract

Phalaris minor is a major weed of wheat crop which has evolved resistance against herbicides. Isoproturon is the most accepted herbicide developed resistance in 1992. Later, introduced herbicides also developed resistance and cross-resistance to their respective binding sites. Isoproturon binds at the QB binding site of the D1 protein of photosystem-II (PS-II), which blocks the electron transfer in photosynthesis. In this work, we have carried out a series of computational studies to prioritize the promising herbicides against D1 protein of P. minor. Through the computational studies, twenty-four lead molecules are prioritized which have shown a higher binding affinity and inhibition constant than the reference ligand molecule. The binding and conformational stability of docked complexes was evaluated by molecular dynamics simulations and binding free energy calculations i.e., MM/PBSA. A list of amino acids such as Ala225, Ser226, Phe227, and Asn229 present in the binding site of protein is obtained to be playing an important role in the stability of the protein-lead complex via hydrogen bond and π-π interactions. Binding free energy calculation revealed that the selected lead molecule binding is energetically favorable and driven by electrostatic interactions. Among 24 leads, computational results have uncovered eight promising compounds as potential herbicides which have shown comparable physiochemical profile, better docking scores, system stability, H-bond occupancy, and binding free energy than terbutryn, a reference molecule. These prioritized molecules were custom synthesized and evaluated for their herbicidal activity and specificity through whole plant assay under laboratory-controlled conditions. The lead molecule ELC5 (6-ethoxy-4-N-(2-morpholin-4-ylethyl)-2-N-propan-2-yl-1,3,5-triazine-2,4-diamine) has shown comparable activity to the reference herbicide(isoproturon) against P. minor.

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Acknowledgements

The authors of this manuscript acknowledge Prof. Krishna Mishra, Indian Institute of Information Technology Allahabad, and Prof. R. S. Rathore HOD, Dept. of Bioinformatics, for extending all possible support in the completion of this research work.

Funding

The authors acknowledge the funding supported by the Science and Engineering Research Board, India file No.YSS/2015/001662.

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Authors and Affiliations

  1. Department of Bioinformatics, School of Earth Biological and Environmental Sciences, Central University of South Bihar, Gaya, India, 824236, Bihar

    Nandan Kumar, Priyanka Rani & Durg Vijay Singh

  2. Department of Computer Science, School of Mathematics, Statistics and Computer Science, Central University of South Bihar, Gaya, India, 824236, Bihar

    Shikha Agarwal

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  1. Nandan Kumar
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  2. Priyanka Rani
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Contributions

D. V. Singh conceived and supervised the study. N. K. and P. R. performed the calculations and experiments. N. K. and S. A. interpreted the results and writing of the manuscript is done by all the authors.

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Correspondence to Durg Vijay Singh.

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Kumar, N., Rani, P., Agarwal, S. et al. 6-Ethoxy-4- N-(2-morpholin-4-ylethyl) -2-N-propan-2-yl-1,3, 5-triazine-2, 4-diamine endows herbicidal activity against Phalaris minor a weed of wheat crop field: An in -silico and experimental approaches of herbicide discovery. J Mol Model 28, 77 (2022). https://doi.org/10.1007/s00894-021-05006-6

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