ParmFit MetalAA

Overview

MetalAA is the parmfit(method=metalaa) route for a PDB target ion selected with ion_resids. It locates the target ion and identifies its coordination environment: donor atoms are detected among N, O, S, P, Se, F, Cl, Br, I within donor_cutoff (default 2.7 Å). The target ion, its donor residues, and any add_resid entries together form the core. Explicit metal-donor SERIAL pairs can be provided via set_bonded to override automatic recognition.

MetalAA then constructs two models. A large model (core + environment residues within cluster_cutoff) is built for MLIP optimization, RESP charge fitting, and Hessian-based bonded parameterization. Broken peptide boundaries are sealed with ACE/NME caps, and when two selected peptide residues on one chain are at most five sequence positions apart, the intervening residues between them are rewritten as Gly bridges to maintain backbone connectivity. A site model (target metal + final core residues only) is the deployable output; declared NCAA residues outside the site model are folded into the tleap deployment alongside it. RESP charges from the large model are projected onto the site model. In the deployable site model, residue names are changed to compact export codes (e.g. CYM becomes CM1, HID becomes HD1) and atom types are renamed locally: the metal receives M1/M2/..., each direct donor atom receives Z1/Z2/..., while other atoms retain their original forcefield types.

For a worked walkthrough, see the MetalAA tutorial.

Target

ion_resids must identify exactly one ion residue in the input PDB. Use a chain and residue number such as A462, an ion residue name and number such as FE462, or append an altloc label when needed, for example A462A for altloc A. The selected residue must contain a single ion atom recognized by MAPLE. It defines the center for donor detection and metal-site construction; add_resid and set_bonded extend that site without changing the target.

Workflow

The route in outline:

1. Metal-site recognition. Locate the target ion, donor atoms, core residues, and optional user-added residues.
2. Ligand building. For each declared ligand (lig_resids): copy the residue, fit its charges, type it with AmberTools, and register the cofactor frcmod.
3. NCAA building. Declared residues (ncaa_resids) are built with the residue-build components of the NCAA route: one optimized capped conformer, RESP on that conformer, and an antechamber/parmchk2 template — without the α/β pair, Hessian refinement, or TorsionFit of the standalone NCAA route. How the fitted charges enter the deployment depends on placement: a residue that coordinates the metal is fitted freely with the site; a non-coordinating residue inside the large model has its fitted charges frozen into the site RESP; a residue outside the large model keeps its independent charges and is folded into the tleap export.
4. Large model. Build and optimize a large metal-site model for RESP, Hessian, and parameter fitting.
5. RESP charges. Gaussian evaluates the ESP of the optimized large model and AmberTools performs the two-stage RESP fit; the charges are then projected onto the deployable site model.
6. Bonded fitting. Use Seminario or modified Seminario to fit metal-related bond and angle terms.
7. Deployment files. Write site mol2, final metal frcmod, tleap PDB/input, and dry/solvated tleap outputs. MetalAA runs tleap itself; the result block prints the command under Next step.

Core Parameters

For qm_engine, opt_level, QM job resources, and MLIP optimization controls, see the General Settings and QM Reference sections of the main ParmFit page.

ChargeFit

RESP Fixed Charges (chgmod)

The chgmod parameter controls which standard backbone atoms are fixed to their Amber reference charges during RESP fitting. Higher values include more atoms in the fixed set:

Use fixchg_resids to lock entire residues to standard Amber reference charges regardless of the chgmod policy. A listed residue outside the large model is skipped with a warning. Specifying a non-standard residue that lacks a reference charge entry stops the run with an error at the RESP stage.

Input Files

Simple Input

A simple MetalAA job declares method=metalaa inline and lists its ParmFit options in a sidecar config. The ion_resids selector picks the metal ion; ion_charges/ion_mults give the metal formal charge and the cluster multiplicity, and lig_resids/lig_charges declare the cofactor. The example is Case 1 of the MetalAA tutorial, which provides the input files and 4ZF6.pdb. There the heme carries −4 — the porphyrin dianion (−2) plus two deprotonated propionates — and Fe(III) +3 with the thiolate −1 gives the large-model charge −2; use the charge that matches the protonation state of your own cofactor.

#model=uma(size=uma-s-1p1)
#parmfit(method=metalaa,input=MetalAA1.in)
#device=gpu0

PDB 4ZF6.pdb

# MetalAA route settings; declare method=metalaa in #parmfit(...) and reference this file via input=
# Only non-default entries are listed; the generated parmfitrun.in shows every resolved value.

ion_resids=A462
ion_charges=3
ion_mults=6
lig_resids=A461
lig_charges=-4
bonded=seminario
chg_level=PBE1PBE/def2SV

Full External Input

For a more complex setup, keep the MAPLE launcher short and move ParmFit parameters into an external .parmfit file. Declare method=metalaa inline together with input=; the external config must not set method=. The PDB remains in the MAPLE input.

#model=uma(size=uma-s-1p1)
#parmfit(method=metalaa,input=MetalAA.parmfit)
#device=gpu0

PDB 4ZF6.pdb

Full ParmFit config

# QM reference
iqm=false
qm_engine=g16
opt_level=B3LYP/def2SVP
opt_route=
qm_nproc=8
qm_mem=24

# RESP charges
resp_backend=gaussian
chg_level=PBE1PBE/def2SVP
chg_route=
chgmod=1
fixchg_resids=

# Force field, water, ion, and bonded fitting
pro_ff=ff14SB
wat_ff=tip3p
ion_ff=12_6
bonded=mseminario
vib_scale=1.0

# MLIP geometry optimization controls
opt_max_iter=256
opt_max_step=0.2

# MetalAA site selection
ion_resids=A462
ion_charges=3
ion_mults=6
add_resid=
set_bonded=
cluster_cutoff=3.0
donor_cutoff=2.7
keep=

# Coordinating ligands, built as small molecules
lig_resids=A461
lig_charges=-4
lig_mults=1
lig_chgfit=abcg2
lig_chglevel=HF/6-31G(d)
lig_chgroute=

# Noncanonical residues in the site, built with the NCAA residue-build components
ncaa_resids=
ncaa_charges=
ncaa_resnames=
ncaa_mults=
ncaa_chgfit=resp
ncaa_chglevel=HF/6-31G(d)
ncaa_chgroute=

Output Files

• <base>_work/<base>_metal_large_raw.pdb and <base>_work/<base>_metal_large_opt.pdb: Large model before and after optimization.
• <base>_work/<base>_metal_site_opt.pdb and <base>_work/<base>_metal_site.mol2: Deployable metal-site model.
• <base>_work/<base>_metal.frcmod: Final metal/cofactor frcmod file.
• <base>_work/<base>_metal_tleap.pdb, <base>_work/<base>_metal_tleap.in, and <base>_work/<base>_metal_tleap.out: tleap deployment and validation files.
• <base>_work/<base>_metal_tleap_dry.* and <base>_work/<base>_metal_tleap_solvated.*: dry and solvated topology/coordinate outputs.
• <base>_work/metalaa/: Gaussian ESP, RESP, and intermediate charge-fitting files.
• <base>_work/lig/<tag>/: Per-ligand small-molecule parameterization (antechamber build and parmchk2 frcmod).
• <base>_work/ncaa/<tag>/: Per-residue NCAA builds for declared ncaa_resids entries.

Requirements and Limits

• Current MetalAA is intended for a single metal center; a second ion inside the donor cutoff is not supported.
• Ligand or cofactor residues without reliable atom types should be declared through lig_resids (small-molecule build) or ncaa_resids (NCAA residue build: one conformer, RESP, AmberTools template).
• When automatic donor detection is not sufficient, use set_bonded to provide explicit metal-donor serial pairs.