Energy restraints and PES modification design

[leeping]

I'm planning to work on this after finishing the transition state feature.

Mode 1: Harmonic Energy restraint on degrees of freedom previously used for constraints

• User can provide a harmonic force constant at the end of the string, leading to a harmonic restraint being created instead of an exact constraint.
• Related feature: Scan groups. User can provide $group markers before each constraint inside of a $scan block to ensure that constraints within a group are being scanned in 1D with their values changing simultaneously. It should look like $group n_steps and the constraints within a group only need to provide initial and final values.

Mode 2: General energy modification

In geomeTRIC:

• User is required to provide a PDB file and an OpenMM system XML file --perturb perturb.xml

Why not pass a force field .xml file? Requires too much legwork to get things working. For example:

• Need to make residue templates to match PDB file
• Requires making distinction between bonded and nonbonded forces
• Not easy to assign a restraint to only one degree of freedom in the system

Build a tool in geomeTRIC that assists with creating mod.xml

• This should be an “input file” tool because interactive tools are hard to automate
• "Freeze, set, scan" are not available. Interactions that involve restraints to reference values can only use the current structure.
• The form of the restraint energy function:
  • Option 1: Restraint is harmonic and a single force constant parameter should be provided.
  • Option 2: Restraint is a custom function and all needed parameters should be provided.
    • Advantage - user can define flat bottomed potentials.
    • Disadvantage - lots of room for error.
  • Option 3: A few presets are provided (harmonic being one of them).
  • There is no option to define different parameters based on element or particle number
    (don’t want to worry about combining rules or parameter lookup tables).
• The user can create restraints for:
  • A single atom selection : Applies a harmonic restraint to selected atoms or all atoms
    • Done via CustomExternalForce.
  • A pair atom selection : Applies a harmonic restraint to all pairs from 2 selections, or all atom pairs
    • Done via CustomNonbondedForce.
  • Three atoms : Applies a harmonic restraint to selected atom triplets (angle) or all angles detected from bond graph
    • Done via CustomAngleForce.
  • Four atoms : Applies a harmonic restraint to selected atom quartets (dihedral) or all dihedrals detected from bond graph
    • Done via CustomTorsionForce.
• Custom force presets are also possible but infinite customization is only available through coding
  • Modification for hydrogen bonding prevention - this is what I actually want to do

Implementation:

• Uses OpenMM
• A new Engine should be created that contains the base Engine and an OpenMM engine to compute the energy modifier
• Optimizations should use the “base + modifier” PES but the “base” energies and forces should also be reported