461829 Gold Nanoparticles Change Human Serum Albumin without Denaturing It: A Computer Simulation Study

Tuesday, November 15, 2016: 9:02 AM
Yosemite A (Hilton San Francisco Union Square)
Qing Shao, Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC and Carol K. Hall, Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC

Excitement about the applications envisioned for nanomaterials in energy, medicine and electronics is tempered by concerns about their toxicity. The toxicity of nanomaterials is believed to be closely related to their ability to denature proteins. This work investigates how binding to a gold nanoparticle with a diameter of 4.0 nm affects the structure and flexibility of human serum albumin. Nanomaterials are considered less toxic if they let proteins remain folded. However, the results of our computer simulations argue that nanomaterials can still induce toxicity even if they do not denature proteins. We identify four binding complexes between the gold nanoparticle and human serum albumin in a brute-force search process using an implicit-solvent coarse-grained model. We then investigate the structural and dynamic properties of the albumin protein within the complexes in explicit solvent using atomistic molecular dynamics simulations. The results show that although the albumin protein remains folded in the simulations, many of its residues change their flexibility and secondary structure. Analysis of these changes shows that the binding of a nanoparticle can alter the flexibility and secondary structure of a protein significantly without denaturing it. The allosteric effect plays a vital role in spreading the impact of a nanoparticle throughout the whole protein. Our simulations suggest that keeping a protein folded does not guarantee a nanoparticle’s safety.

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