Molecular dynamic simulation of Trastuzumab F(ab')2 structure in corporation with HER2 as a theranostic agent of breast cancer

S. Hermanto, M. Yusuf, A. Mutalib, Sumi Hudiyono Pws

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2 Citations (Scopus)


Trastuzumab as intact IgG are well researched for theranostic agent in HER2 overexpressed breast cancer. However, due to the relatively large of molecules it is slowly moved and weak penetration of the target cells. Fragmentation of trastzumab has been developed by pepsin cleavages to get the F(ab')2 fragments. To observe the stability and accessibility of F(ab')2 structure in corporation with HER2 (human epidermal growth factor receptor-2), the structure of antibody modeling had been developed with 1IGT as a template. Molecular dynamics (MD) of the F(ab')2 structure simulation has been done in the aqueous phase with AMBER trajectories for 20 ns. Computational visualization by VMD (Visual Molecular Dynamics) were applied to identify binding site interaction details between trastuzumab F(ab')2 and HER2 receptor. The results of MD simulations indicated that the fragmentation of trastuzumab F(ab')2 did not change the structure and conformation of F(ab')2 as a whole, especially in the CDR (Complementarity Determining Region) area. SASA (solvent accessibility surface area) analysis on lysine residues showed that formation of conjugate DOTA-F(ab')2 predicted occur on outside of the CDR regions so its not interfered with binding affinity for the HER2 receptor. The molecular dynamic simulation of DOTA-F(ab')2 with HER2 receptor in aqueous system generated ΔGbinding more highly (15.5066 kkal/mol) than positive control HER2-Fab (-45.1446 kkal/mol).

Original languageEnglish
Article number012005
JournalJournal of Physics: Conference Series
Issue number1
Publication statusPublished - 17 Apr 2017
EventInternational Symposium on Bioinformatics, Chemometrics and Metabolomics, ISBCM 2016 - Bogor, Indonesia
Duration: 18 Oct 2016 → …

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