vtlim / dihedral-scan

Compute dihedral scan in some molecule, such as to compare an MM force field to QM results.

Light validation of small molecule force field

Last updated: Mar 07 2019
This instructions list subdirectory names for each step for easier locating of relevant files.

Contents

Brief high-level overview of contents in this repository.

.
├── 01_setup
│   ├── 01_setup-dihedrals.tcl
│   ├── 02_pdbPsiInput.sh
│   ├── 03_NAMDinput.sh
│   ├── minimize.inp
│   └── psfgen
│       ├── psfgen-02
│       ├── psfgen-03
│       └── psfgen.tcl
├── 02_analysis
│   ├── 01_atom-labels
│   ├── 02_parse-diheds
│   └── view_namd_scan.tcl
├── dihed_namd
│   ├── 0
│   └── 5
├── dihed_psi4
│   ├── 0
│   │   ├── dihed-0.pdb
│   │   └── mp2-631Gd
│   └── 5
│       ├── dihed-5.pdb
│       └── mp2-631Gd
├── init_namd
├── init_psi4
├── LICENSE
├── psf_from_charmm
├── README.md
└── slurm_scripts

19 directories, 65 files

I. Force field generation

1. Drew structure in MarvinSketch.

   • Saved as Tripos mol2 for CGenFF.

2. [./cgenff] Uploaded to CGenFF, and downloaded resulting .str file.

   • Unchecked "Guess bond orders from connectivity"
   • Unchecked "Include parameters that are already in CGenFF"
   • Unchecked "Use CGenFF legacy v1.0"
   • Edited the name after RESI to GBIN (use the resname code you want)
   • NOTE: CGenFF website summary page says current FF version is 3.0.1 but this is NOT correct according to str header and Mackerell website.

3. [./cgenff/] Generate PDB file for NAMD.

   • convertExtension.py
   • python convertExtension.py -i gbi-neutral-cgenff.mol2 -o gbi-neutral-cgenff.pdb
   • Checked out the structure in VMD. Marvin did not generate a very good starting structure.
   • Edited PDB to have resname and segname of GBIN.

4. [./01_setup/psfgen/] Generate PSF file for NAMD.

   • Command: vmd -dispdev none gbi-neutral-cgenff.pdb -e psfgen.tcl > psfgen.out
   • NOTE: See psf_from_charmm directory in this repo for an alternate approach.

5. [./02_analysis/01_atom-labels/] Label atom numbers in VMD. Generate image to refer to later when altering atom types or choosing atoms for dihedral scan.

   • Modify displayed label at Graphics > Labels > Properties > Format to %a::%t
   • Did this one by one but probably could write Tcl script if larger ligand, based on label textformat Atoms 15 { %a::%t }
   • Do not render as (Tachyon, Postscript) since messes up label location. Cluster super slow, so I just screenshotted.

II. Comparison of QM and MM minimum energy structures

NOTE: This section walks through NAMD minimization before QM minimization. If you want QM calcns on your input structure to CGenFF, the init_psi4/opt_mmff.py script may be helpful. It uses the Quanformer package: https://github.com/MobleyLab/quanformer. However, instead of installing the package, you can download the relevant modules from Github and call similar to here.

6. [./init_namd/] Minimize in NAMD.

   • Do this prior to full scan bc starting Marvin coordinates are garbage.

7. Analyze minimized MM structure in VMD. This will be used as input for QM.

   • Load the .psf file and minimized .coor file.
   • If structure needs manual rearrangement (e.g., if not planar when you know it should be, or if you want to consider additional conformations)
     • VMD move atom: press 5, click atom, move atom with mouse.
     • VMD move group of atoms: create new representation (Graphics > Representations) with selected atoms, press 9, rotate/translate with mouse.
     • VMD manual
   • For each structure, File > Save coordinates > select all atoms. Save as .pdb or .xyz format.

8. [./init_psi4/] Geometry minimize with QM using Psi4.

   • Directly lifted coordinates from previous step for Psi4 input file.

9. Compare minimized structures from steps 6 and 8 in VMD.

   • Based on agreement of minima structures, you may need to change atom types. In that case, remember to regenerate the psf file (step 4).
   • When I added improper terms in str file, it wasn't recognized by psfgen. So I modified the generated PSF directly.
     • In the 2 !NIMPHI: impropers subheading, I added the atom numbers for new impropers (4 atoms/improper).
     • Also incremented subheader value next to NIMPHI by number of impropers added.
     • See example in 01_setup/psfgen/ comparing the PSF in psfgen-02 and psfgen-03 .
   • Also had to fix some of the atom name columns in the last column of generated PDB file bc some were missing.

III. Comparison of QM and MM dihedral scan profiles

10. Analyze molecule to prepare for dihedral scan.

    • Identify atoms to be rotated.
      • Example: H9, N5, C8, N4, H8, H7, H6, not N3
    • Identify PDB numbers corresponding to above.
      • Example: 22 13 11 12 21 20 19
    • Determine which atoms will define dihedral angle.
      • Example: N2 C7 N3 C8 (8 9 10 11)

11. [./01_setup/] Generate structures for dihedral scan.

    • Subtract 1 from PDB numbers for use in Tcl script with VMD, and for NAMD
    • But use the PDB numbers as in when restraining in Psi4
    • Edit and run 01_setup-dihedrals.tcl
      • Name of input PDB
      • Where output PDBs are written
      • Atom numbers of whole group to be rotated
      • Atom numbers of the four atoms to define dihedral.
        • NOTE: Order matters. Atoms should be listed in order, with central atoms in middle. If [A B C D] does not work, try [D C B A].
    • Edit and run 02_pdbPsiInput.sh
      • Main directory location
      • Name of theory subdirectory
      • Atom numbers to be frozen
      • Method and basis set used
      • Any other desired QM parameters
    • Edit and run 03_NAMDinput.sh
      • Main directory location
      • Name of reference input file
      • Atom numbers of the dihedral for restraint

12. Run the QM and MM jobs.

13. [./02_analysis/02_parse-diheds] Analyze scans.

    • Get NAMD dihedral output angle from .coor files.
      • vmdt -e ../12_analysis/get_namd_diheds.tcl -args /DFS-B/DATA/mobley/limvt/3_neutral/11_setup-namd/psfgen-03/gbin_psfgen.psf 7 8 9 10
      • May want to sort resulting dat file (in vim: :sort n).
    • Compute/draw the profiles.
      • python dihed_parser.py --qdir /path/to/qm_results/ --qfile output.dat --mdir /path/to/mm_results/ --mfile minimize.out --show --save

14. [./02_analysis/03_view] View results.

    • TODO: add view scripts

Notes to VTL

Sources of example materials:

• PSF: /DFS-B/DATA/mobley/limvt/3_neutral/11_setup-namd/psfgen-03/gbin_psfgen.psf
• PDB: /DFS-B/DATA/mobley/limvt/3_neutral/init_namd2/03_point-out/final.pdb
• init NAMD input: /DFS-B/DATA/mobley/limvt/3_neutral/init_namd2/minimize.inp
• init Psi4 input: /DFS-B/DATA/mobley/limvt/3_neutral/init_psi4/01_mp2-631Gd/input.dat
• dihed NAMD input: /DFS-B/DATA/mobley/limvt/3_neutral/dihed_namd
• dihed Psi4 input: /DFS-B/DATA/mobley/limvt/3_neutral/dihed_psi4