- Kleinjung, J, Fraternali, F - Urea-water solvation forces on prion structures
- J Chem Theor Comp 8:3977-3984, 2012
Solvation forces are crucial determinants in the equilibrium between the folded and unfolded state of proteins. Particularly interesting are the solvent forces of denaturing solvent mixtures on folded and misfolded states of proteins involved in neuro-degeneration. The C-terminal globular domain of the ovine prion protein (1UW3) and its analogue H2H3 in the α-rich and β-rich conformation were used as a model structures to study the solvation forces in 4 M aqueous urea by Molecular Dynamics. The model structures display very different secondary structure and solvent exposure. Most protein atoms favour interactions with urea over interactions with water. The force difference between protein-urea and protein-water interactions correlates with hydrophobicity, i.e. urea interacts preferentially with hydrophobic atoms, in agreement with results from solvent transfer experiments. Solvent Shannon entropy maps illustrate the mobility gradient of the urea-water mixture from the first solvation shell to the bulk. Single urea molecules replace water in the first solvation shell preferably at locations of relatively high solvent entropy.
- Kleinjung, J, Scott, W R P, Allison, J R, van Gunsteren, W F, Fraternali, F - Implicit solvation parameters derived from explicit water forces in large-scale Molecular Dynamics simulations
- J Chem Theor Comp 8:2391–2403, 2012
Implicit solvation is a mean force approach to model solvent forces acting on a solute molecule. It is frequently used in molecular simulations to reduce the computational cost of solvent treatment. The free energy of solvation and the associated solvent-solute forces can be approximated by a function of the solvent-accessible surface area of the solute and an atom– specific solvation parameter σiSASA. An analytical formula for the determination of σiSASA parameters through matching of explicit and implicit solvation forces is proposed. Using the results of Molecular Dynamics simulations of 188 topologically diverse protein structures in water and in implicit solvent, the σiSASA parameters for atom types i of the standard amino acids in the GROMOS force field have been determined. A simplified representation based on groups of atom types σg was obtained via partitioning of the atom–type σiSASA distributions by dynamic programming. Three groups of atom types with well separated parameter ranges were obtained, and their performance in implicit versus explicit simulations was assessed. The list of domain names and the solvent forces are available below.
The list of domain names is given here:
The solvent force repository contains the explicit water forces and the protein configurations of the 188 domains used in the study:
The repository can be extracted with the commands 'bunzip2' and 'tar -xvf'. The repository is large (2.1 GB compressed)! The program 'wget' is recommended for downloading the repository.