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Protocol for protein benchmark simulations

System setup

Chapin Cavender

• Protein starting coordinates

  • Folded proteins

    • 1) PDB structure

    • 2) Randomly sample from published MD trajectory

  • Disordered proteins

    • 1) Extended structure (phi, psi = 180 deg, 180 deg)

    • 2) Randomly sample from PED ensemble

• Thermodynamic state

  • Pressure, temperature, pH, ionic strength

  • 1) Same for all systems: 1 atm, 298 K, pH 7, 150 mM NaCl

  • 2) Match conditions of NMR experiment

    • Provenance of observables difficult to track

    • Observables for the same protein measured in experiments with different conditions

    • Some NMR experimental conditions difficult to model, e.g. D₂O

• Solvent

  • Rhombic dodecahedron with 10 Å padding for folded proteins and 12 Å padding for disordered proteins

  • Neutralize with counterions then add ion pairs to match bulk salt concentration using SLTCAP

• Protomers and tautomers

  • 1) Most populated protonation state at pH, choose HIE for neutral HIS

  • 2) Assign protomers from H++

Dynamics

• Nonbonded model - match SMIRNOFF spec for Sage

  • PME electrostatics with 9 Å cutoff and 5/6 1-4 scaling

  • 12-6 LJ with 9 Å cutoff, 1 Å switch width, and 1/2 1-4 scaling

• Integrator

  • Langevin with frequency 1 ps⁻¹

  • Time step 2 fs with SHAKE

• Barostat

  • Monte Carlo barostat with frequency 100 steps

• Equilibration

  • 1 ns equilibration with 1 fs timestep, 5 ps⁻¹ Langevin frequency, 20 step barostat frequency, and 1 kcal mol⁻¹ Cartesian restraints on protein atoms

  • Post-process production trajectory to determine burn-in time