Parmfit NCAA

Overview

NCAA is the parmfit(method=abinitio) route for a noncanonical amino acid residue classified as a protein residue. It builds a capped ACE-target-NME model, where the backbone and caps are frozen during optimization so that only the sidechain R-group relaxes. Two initial backbone conformers (α and β) are generated, multiconformer RESP charges are fitted, AmberTools prepin/frcmod templates are created, and bond/angle terms plus sidechain torsions are refined. Deployment is validated with tleap.

Initial Prepare

The input PDB should carry reasonable protonation states. The target residue must contain properly named backbone atoms (C, O, N, H, CA) and at least one sidechain heavy atom bonded to CA. NCAA relies on these standard names for chirality detection, backbone freezing, and mainchain-path inference.

Important

Use method=abinitio, not a separate NCAA method keyword. MAPLE enters this route only when the selected target is recognized as a protein residue in the PDB.

Workflow

Target identity. Locate the target residue and detect backbone, sidechain anchor, and chirality.
Capped model. Build and optimize an ACE-target-NME representative model.
RESP conformers. Generate alpha and beta capped conformers and run multiconformer RESP.
AmberTools template. Run antechamber, prepgen, and parmchk2 to create initial prepin/frcmod files.
Parameter refinement. Apply Seminario/mSeminario to bond/angle terms and TorsionFit to target-residue sidechain torsions.
Deployment. Write refined prepin/frcmod, processed protein PDB, tleap input, and tleap validation outputs.

Core Parameters

Parameter	Default	Description
`target`	Required	PDB residue selector for the residue to parameterize.
`cmo`	`0 1`	Total charge and multiplicity for the target residue model.
`rn`	`MOL`	Output residue name used in prepin/frcmod and processed PDB files.
`prom`	`ff14SB`	Protein force field model, commonly `ff14SB` or `ff19SB`.
`watm`	`tip3p`	Water model for tleap deployment and RESP radii context.
`ionm`	`12_6`	Ion parameter set name passed to tleap deployment; NCAA does not enforce a fixed whitelist.
`bonded`	`mseminario`	Bond/angle refinement: `mseminario`, `seminario`, or `none`.
`vib_scale`	`1.0`	Force constant scaling factor for Seminario/mSeminario Hessian-based fitting
`chg_level`	`HF/6-31G(d)`	Gaussian level for RESP ESP generation. Always active regardless of `iqm`.
`iqm`	`false`	Use external QM reference geometry/Hessian/torsion references beyond the RESP jobs. See the main Parmfit page for details.

For TorsionFit parameters, QM job resources, MLIP optimization controls, and levels of theory, see the TorsionFit, General Settings, and QM Reference sections of the main Parmfit page.

Preserving original GAFF2 parameters

Bond/angle and torsion refinement are controlled separately. Setting bonded=none keeps the initial BOND/ANGLE terms; setting torsionfit=false keeps the initial DIHE terms. When either refinement is enabled, atom types are automatically reassigned (MAPLE Z0/Z1, etc.).

TorsionFit

NCAA uses a center-bond filter that restricts torsion fitting to target-residue sidechain torsions only; backbone–backbone and cap torsion bonds are excluded. For residues with particularly complex sidechains, consider setting torsionfit=false and relying on the original GAFF2 torsion parameters, or use torsion_bonds to refine specific dihedrals selectively. NCAA disables torsion ensemble targets internally; see the main Parmfit page for scan and refinement parameter details.

Peptide Boundary Terms

When the NCAA residue is inserted as a custom template, MAPLE dynamically generates ProteinFF-GAFF2 cross-terms at both peptide boundaries: the head side (prev_C–target_N) and the tail side (target_C–next_N). These include exact BOND, ANGLE, and DIHE terms that connect the custom template atom types to the neighbouring standard protein residue atom types.

Full Parmfit Input

Checked-in Parmfit config: examples/parmfit/NCAA.parmfit. Use it from a MAPLE input with #parmfit(method=abinitio,input=NCAA.parmfit).

NCAA.parmfit

method=abinitio
target=A123
cmo=0 1

# QM reference
iqm=false
qm_engine=g16
opt_level=B3LYP/def2-SVP
sp_level=B3LYP/def2-SVP
opt_route=em=gd3bj
sp_route=
qm_mode=1
qm_compare=false
qm_nproc=8
qm_mem=24

# RESP charges
resp_backend=gaussian
chg_level=HF/6-31G(d)
chg_route=

# Residue, force field, water, ion, and bonded fitting
rn=MOL
prom=ff14SB
watm=tip3p
ionm=hfe
bonded=mseminario
vib_scale=1.0

# NCAA capped/RESP conformer optimization controls
opt_max_iter=256
opt_max_step=0.2

# TorsionFit
torsionfit=false
torsion_bonds=
torsion_steps=36
backend=cgbs
constraint_mode=projected
stage1_weights=true
torsion_refine_rounds=3
torsion_refine_max_iter=256
torsion_refine_tol=1.0e-6
torsion_ensemble=false
torsion_ensemble_ratio=0.3
torsion_ensemble_weight=0.5
report_debug=false

Output Files

<base>_work/<rn>.prepin and <base>_work/<rn>.frcmod: Initial AmberTools residue template files.
<base>_work/<rn>_maple.prepin and <base>_work/<rn>_maple.frcmod: Refined MAPLE residue template and parameter files.
<base>_work/<base>_ncaa_tleap.pdb and <base>_work/<base>_ncaa_tleap.in: Processed protein PDB and tleap input.
<base>_work/<base>_ncaa.prmtop, <base>_work/<base>_ncaa.inpcrd, and solvated PDB outputs: tleap validation products.
<base>_work/ncaa/: RESP, conformer, antechamber, prepgen, and torsion-refinement intermediates.

Requirements and Limits

The target must be a protein residue with enough backbone and sidechain identity for capping and chirality detection.
RESP jobs use the Gaussian backend.
TorsionFit is restricted to target-residue sidechain-related center bonds and does not fit peptide backbone torsions.