Abstract

Tomato is one of the most cultivated and highly consumed crops globally, often hampered by a soil borne fungal pathogen Fusarium oxysporum f. sp. lycopersici causing vascular wilt. Pathogenic proteins like formyl peptide receptor 1, mitogen-activated protein kinase encoding, class V chitin synthase and tomatinase have been investigated in this study using molecular modeling, docking and dynamics-based techniques as potential molecular targets during pathogenesis or defence response. Thus, MODELLER 9.16 was used to predict three dimensional structures of the above proteins further refined and minimized. To get the new and dominant lead molecule, Trichoderma secondary metabolites were extracted from Trichoderma biomass isolated from healthy rhizospheric soil from an infected wilt field. The crude ethyl acetate extracts were purified and analyzed by gas chromatography-mass spectrometric analysis followed by in silico and in vitro analysis. Eventually, 85 compounds were selected in the first phase selection criteria for docking and it was found that molecule 1-allyl-4-[(3,4-dimethoxy-phenyl)-(1-thiophen-2-ylmethyl-1H-tetrazol-5-yl)-methyl]-piperazine and p-dihydroartemisinin oxymethyl benzoic acid were showed highest binding affinity towards Fusarium proteins as their binding energy fall in range of between -7.64 to -8.76 Kcal/mol. To increase the efficiency of molecules the five derivatives were designed and based upon the docking results, three potential derivates undergone for molecular dynamic studies over 100 ns against pathogenic proteins. Thus, aiding future development of the designed potent derivatives can be explored for experimental validation against the Fusarium pathogenic proteins to complement the current management techniques. This improvised new strain of Trichoderma species would assist in controlling disease effectively, especially against soil-borne pathogens.