In the molecular dynamics simulations, the
atomic interactions were described by the AMBER99SB-ILDN
25 (link) force field, extended with optimized parameters
for the triphosphate chain of GTP.
26 (link) Long-range
electrostatic interactions were treated via the particle mesh Ewald
method.
27 (link) The short-range nonbonded interactions
(e.g., electrostatics and van der Waals interactions) were cut off
at 1.1 nm.
All of the equilibration was performed with GROMACS
v.4.6.5.
28 (link) The leap-frog integrator was
used with a time step of 2 fs. Temperature was kept constant at 310
K using the v-rescale thermostat
29 (link) using
two temperature coupling groups: the first group consisted of the
protein, GTP and Mg
2+, while the second group consisted
of water, Na
+, and Cl
–. The pressure
was kept constant using the Parrinello–Rahman barostat
30 (link) at a pressure of 1 bar. All bond lengths were
constrained using the LINCS algorithm.
31 (link)The 100 ns production runs were performed with OpenMM (7.1.0.dev-5e53567).
32 (link) The constraints were changed to only affect
bonds including a hydrogen atom, using SHAKE,
33 (link) the integrator was the Velocity Verlet with velocity randomization
(VVVR) integrator
34 (link) from OpenMMTools v.0.14
35 (link) and the barostat was the Monte Carlo barostat.
36 (link) The production simulations were run using the
CUDA platform of OpenMM on NVIDIA
GeForce GTX TITAN X GPUs.
Roet S., Hooft F., Bolhuis P.G., Swenson D.W, & Vreede J. (2022). Path Sampling Simulations Reveal How the Q61L Mutation Alters the Dynamics of KRas. The Journal of Physical Chemistry. B, 126(48), 10034-10044.