Completely freeze the ligands in place, so that the host coordinates aren't minimized to different poses than what the system expects downstream.
Delete clashy waters upon system set up, which resolves issues with cagey molecules (where water could be trapped inside)
Adds pre-equillibration to reduce 'air bubbles' in the simulations (does not modify ligand).
Centers solvent systems around ligands when building systems to ensure consistent water box construction. IE such that the ligands don't get placed in the margin setup within the box and minimization of solvent boxes are dependent on the starting point of ligands.
Decoupling is still required due to eps values of 0.0 in protein hydrogens, but now minimize at lambda = 0.1 and 0.0 (can be adjusted), rather than lowering down from 1.0
Systems tested
Verified that the following public systems and the corresponding ligands minimize in the solvent/complex (including through bisection).
Sets taken from
Hif2a
PFKFB3 - Added to the tests since it has a clash that blows up
TYK2
CDK8 - The original set that required our previous implementation of minimization
Systems tested
Verified that the following public systems and the corresponding ligands minimize in the solvent/complex (including through bisection).
Sets taken from
Todo