ASM 2019

Poster (P8)


Molecular dynamics and metadynamics study for binding and decorpoartion of plutonium in serum transferrin.

Lokpati Mishra1#, P. D. Sawant, and Tusar Bandyopadhyay 2

1 Radiation Safety Systems Division, BARC, Mumbai &#HomiBhabha National Instituite Mumbai,

2Theoretical Chemistry Section, BARC, Mumbai

Email lokpati[at]barc.gov.in

 

There is a probability of plutonium (Pu) intake by radiation workers either by inhalation, cuts/wounds or ingestion, in spite of stringent safety measures at nuclear facilities handling Pu. On entry into the human body, transportation of Pu to various organs/cells is mainly carried through iron carrying protein serum transferrin (sTf), which finally delivers it into cells by receptor-mediated endocytosis. Here we report MD simulations of the binding/unbinding behaviour of tetravalent plutonium ion with sTf. Four sets of 100 ns MD simulations were carried at four different protonation states of the protein, with pH ranging between extracellular (pH=7.4) and intracellular (pH=5.5) medium. The results suggest that binding motif of Pu is different to that of native iron in sTf. Upon protonation of synergetic carbonate ion and one of the tyrosine (TYR-188), Pu ion is released from the binding pocket of sTf. Hydroxypyridinone (HOPO) and catechol (CAM) have been docked at the binding site (BS) of the protein at extracellular pH condition in order to decorporate Pu from the BS using well-tempered metadynamics. Pu binding at BS at extracellular pH condition is found to be so strong that it was not detached form BS in the absence any ligand, or, even with docked HOPO till 200 ns. However, with the help of CAM ligand, Pu was detached from the BS after 55ns under similar simulating conditions. These findings show that CAM based derivatives can be potential chelating agents for decorporation of Pu form transferrin protein. These findings will help in better understanding of the biochemical behaviour of plutonium inside our body and also aid in developing the protocol for its decorporation from human body.

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