Cancer is the world’s dreaded disease and its prevalence is expanding globally. The study of integrated molecular networks is crucial for the basic mechanism of cancer cells and its progression. During the present investigation we have examined different flavonoids that targets protein kinases B (AKT1) protein which exerts their anticancer efficiency intriguing the role in cross talk cell signalling, by metabolic processes through in-silico approaches. Molecular dynamics simulation (MDS) was performed to analyse and evaluate the stability of the complexes under physiological conditions and the results were congruent with molecular docking. This investigation revealed the effect of a point mutation (W80R), considered based on their frequency of occurrence, with AKT1. The ligand with high docking scores and favourable behaviour on dynamic simulations are proposed as potential W80R inhibitors. A virtual screening analysis was performed with 12000flavonoids satisfying the Lipinski’s rule of 5 according to which drug-likeness is predicted based on its pharmacological and biological properties to be active and taken orally. The pharmacokinetic ADME (adsorption, digestion, metabolism and excretion) studies featured drug likeness. Subsequently, a statistical significant 3D-QSAR model of high correlation coefficient (R2) with 0.992 and cross validation coefficient (Q2) with 0.6132 at 4 component PLS (partial least square) were used to verify accuracy of the models. The molecular dynamics simulation of this study showed that the compound is Taxifolin (I-UPAC namely2-(3,4-dihydroxyphenyl)-3,4 –dihydro-2H-chromene-5,7-diol of C15H14O5, of CID ID-443637 evidenced a better interaction with docking score (-9.63Kcal/mol) exhibited the binding affinity with W80R mutant protein thus reflecting that natural inhibitor can be considered for experimental evaluation which provides targeted insights for new combination of drugs in forming a network in pharmacology.