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Protein Folding in Solution
In this exercise, you will calculate the protein folding free energy in aqueous solution using thermodynamic integration, a method based on molecular dynamics (MD). The protein will be described by the empirical force field, CHARMM, http://mackerell.umaryland.edu/charmm_ff.shtml
Background
A model protein you will have to deal with is the alanine decapeptide. The folding/unfolding will be achieved by fixing the distance between the end carbon atoms in the chain: atoms 7 and 98. This distance is called a collective variable. At each distance one runs the MD simulation (constrained MD) to extract the time-averaged forces acting on the collective variable, $F(x)$. Then, a free energy difference can be calculated via thermodynamic integration (TI):
\begin{equation} \Delta A = -\int_a^b F(x)\, dx \end{equation}
Here $a$ and $b$ are the initial and the final values of the collective variable. TI is a general method, which can be applied to a variety of processes, e.g. phase transitions, electron transfer etc.
1. Task: Familiarize yourself
Download the files: deca_ala.tar.gz
deca_ala.pdb (protein data base) file contains the coordinates
deca_ala.psf (protein structure file) file contains connectivity data
par_all27_prot_lipid.inp contains the force field parameters
md_1836.inp is the CP2K input file
Open the deca_ala.pdb protein data bank format file with vmd. Create a new representation for the protein, e.g. of type Ribbon to observe the alpha-helix.