HER-2 belongs to the human epidermal growth factor receptor (HER) family. Via 
different signal transduction pathways, HER-2 regulates normal cell 
proliferation, survival, and differentiation. Recently, it was reported that 
MCF10A, BT474, and MDA-MB-231 cells bearing the HER2 K753E mutation were 
resistant to lapatinib. Present study revealed that HER-2 mutant K753E showed 
some contrasting behaviour as compared to wild, L768S and V773L HER-2 in complex 
with lapatinib while similar to previously known lapatinib resistant L755S HER-2 
mutant. Lapatinib showed stable but reverse orientation in binding site of K753E 
and the highest binding energy among studied HER2-lapatinib complexes but 
slightly lesser than L755S mutant. Results indicate that K753E has similar 
profile as L755S mutant for lapatinib. The interacting residues were also found 
different from other three studied forms as revealed by free energy 
decomposition and ligplot analysis.