Chignolin Simulations

The initial structure of Chignolin was generated starting from the cln025 peptide, with sequence TYR-TYR-ASP-PRO-GLU-THR-GLY-THR-TRP-TYR. The structure was solvated in a cubic box of 40A, containing 1881 water molecules and two Na+ ions to neutralize the peptide's negative charge. MD simulations were performed with ACEMD, using CHARMM22* force field and TIP3P water model at 350K temperature. A Langevin integrator was used with a damping constant of 0.1 1/ps. Integration time step was set to 4 fs, with heavy hydrogen atoms (scaled up to four times the hydrogen mass) and holonomic constrains on all hydrogen-heavy atom bond terms. Electrostatics were computed using Particle Mesh Ewald with a cutoff distance of 9A and grid spacing of 1A. Ten NVT simulations of 1 ns length were carried out, with a dielectric constant of 80 and temperature of 350K to generate ten different starting conformations for the production runs. Production simulations consisted of 3744 independent simulations of 50 ns, for a total aggregate time of 187.2 µs. All simulations were performed using and adaptive sampling algorithm, where multiple rounds of simulations are performed, and each round the available trajectories are analyzed to select the initial coordinates for the next round of simulations. All simulations were run using the GPUGRID distributed computing platform.