ct3002267_si_001.pdf (2.35 MB)
Counterion Effects on the Denaturing Activity of Guanidinium Cation to Protein
journal contribution
posted on 2012-11-13, 00:00 authored by Qiang Shao, Yubo Fan, Lijiang Yang, Yi Qin GaoThe denaturation of a three-α-helix bundle, the
B domain
of protein A, by guanidinium is studied by molecular dynamics simulations.
The simulation results showed that in GdmCl solution, guanidinium
cations accumulate around the protein surface, whereas chloride anions
are expelled from the protein. In contrast, in GdmSCN solution, both
cations and anions accumulate around the protein surface and the degree
of Gdm+ accumulation is higher than that in GdmCl, suggesting
the cooperativity between the cations and anions in preferential binding.
Moreover, the accumulation of guanidinium around the protein surface
is not uniform, and it prefers to populate near residues with negatively
charged or planar side chains. On the other hand, guanidinium participates
in direct hydrogen bonding with backbone carbonyl groups. Meanwhile,
guanidinium also promotes the hydrogen bonding of water to a backbone
carbonyl group by changing the hydrogen bonding network within solvent.
Therefore, the attack from both water and guanidinium breaks backbone
hydrogen bonds and results in the destruction of secondary structures
of the protein. The stronger accumulation of guanidinium and more
hydrogen bonding from guanidinium in GdmSCN leads to the increase
of its denaturing efficiency compared to GdmCl. In the latter solution,
the ion pairing between Cl– and guanidinium limits
the approach of guanidinium to protein and the hydrogen bonding between
guanidinium and protein, and the main denaturing contributor is the
hydrogen bonding from water.