energy minimization
Maestro 11.5/ Amber18
None
The binding pose of the ligand in 5qc6 chain A was used as a lead. Functional groups were modified to obtain all compounds by using Maestro.
maxcyc = 10000, ntc = 1, ntf = 1, restraintmask = '!:WAT & !@H=', restraint_wt = 100.
The torsion angle was arbitrarily adjusted to accommodate the shape of the binding site and minimized in Maestro.
The modified atoms were further relaxed during the minimization and equilibrations before production runs.
Yes
AM1-BCC/TI
Maestro/Schrödinger,pmemd.GTI,ANTECHAMBER
ff14SB/GAFF2
AM1-BCC charge method
Windows per transformation: 24
Assumed pH 7.0
Typical simulation time per window: 4 ns
timestep: 2fs
shake: on
temp: 298K
lagenvin dynamics with gamma=1.0
NVT
Softcore alpha: 1A
Ligand was built using Maestro/Schrödinger.
Charge derivation: Partial charges were assigned using antechamber with AM1-BCC method, same charges were restrained to same values for the common sub-structures.
Thermodynamic Integration in pmemd/AMBER was used.
Initial ligand and complex structures were adopted from chain B in 5qc6.
Hydrogen atoms of protein were added by Molprobity.
Asp/Glu are deprotonated and Lys/Arg are protonated.
All histidines were neutral and their tautomer states were set as suggested by Molprobity.
ligand and complex structures were properly minimized and equilibrated using typical protocals from Dr. Simmerling's lab.
Charges on the disappearing atoms were turned off first followed by turning off the VDW interactions on the disappearing atoms.
VDW interactions of the appearing atoms were turned on followed by turning on the charges on the appearing atoms.
No
No