Urea and guanidinium chloride denature Protein L in different ways in molecular dynamics simulations

¹ University of Milano

^* To whom correspondence should be addressed. E-mail: tiana{at}mi.infn.it.

Submitted on November 15, 2007
Revised on December 15, 2007
Accepted on 12 February 2008

	Abstract

In performing protein-denaturation experiments, it is common to employ different kinds of denaturants interchangeably. We make use of molecular dynamics simulations of Protein L in water, in urea and in guanidinium chloride to investigate if there are any structural differences in the associated unfolding processes. The simulation of proteins in solutions of guanidinium chloride is complicated by the large number of charges involved, making it difficult to set up a realistic force field. Furthermore, at high concentrations of this denaturant the motion of the solvent slows down considerably. The simulations show that the unfolding mechanism depends on the denaturing agent: in urea the beta-sheet is destabilized first, while in guanidinium chloride it is the -helix. Moreover, while urea interacts with the protein accumulating in the first solvation shell, guanidinium chloride displays a longer-range electrostatic effect which does not perturb the structure of the solvent close to the protein.

Key Words: denatured state, unfolding simulations

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