Resorcyclic acid lactones are synthetic natural product derivatives based on the structure of Hamigeromycin B with the potential for mediating signal transduction in human kinases. The potential biological activity of proteins were studied by computational methods. The goal to develop potential cancer drugs based on Hamigeromycin B emphasizing ease of synthesis, cost-effectiveness, and specificity. Virtual screening is utilized for this project as it is an efficient method for screening multiple compounds with a protein target. 11 analogs were constructed using MOE 2020 and optimized using the AMBER14:EHT force field. These compounds were docked into 26 human kinases in the Protein Data Bank.  The docking sites in each kinase were targeted using the Protein Frustratometer and Evolutionary Trace methodologies to characterize the thermodynamics and evolutionary importance of amino acids for to assess the likelihood of each amino acid residue in the active site to contribute to binding. The lowest binding free energy scores were used to determine the best binding and orientation of each analog. Three kinases were screened with 89 hamigeromycin B analogs obtained from a literature search. Pharmacophore modeling was used to screen each of these compounds based on their structural characteristics as well as the known structure of the receptor. The pharmacophore study identified the best analogs with the strongest binding affinity to JNK3, EGFR and HSP90. Molecular Dynamics simulations were performed on the top three compounds assess their stability and interactions with the receptors

Virtual of hamigeromycin B natural product derivatives in JNK3, EGFR, and Hsp90

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