🔬 PDB/MMCIF toolkit in Molecular Dynamic Simulation workflows

Pre- and post-processing toolkit for PDB/MMCIF structure files in molecular dynamics workflows.

Prerequisites

Always check for the forums of the MD simulation software you are using.

Installation

pip install pdb-md

Usage

❯ pdb-md  --help
                                                                                                                                                                                                                       
 Usage: pdb-md [OPTIONS] COMMAND [ARGS]...                                                                                                                                                                             
                                                                                                                                                                                                                       
 Pre- and post-processing toolkit for PDB/MMCIF structure files in molecular dynamics workflows.                                                                                                                       
                                                                                                                                                                                                                       
╭─ Options ───────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────╮
│ --install-completion          Install completion for the current shell.                                                                                                                                             │
│ --show-completion             Show completion for the current shell, to copy it or customize the installation.                                                                                                      │
│ --help                        Show this message and exit.                                                                                                                                                           │
╰─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────╯
╭─ Commands ──────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────╮
│ select        Select segments from a PDB or MMCIF structure file.                                                                                                                                                   │
│ termini-rm5p  Remove terminal phosphate groups from nucleic acids, e.g. 5' phosphate group from DNA/RNA.                                                                                                            │
╰─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────╯
                                                               

1️⃣ select

Select segments from a PDB or MMCIF structure file

❯ pdb-md select --help
                                                                                                                                                                               
 Usage: pdb-md select [OPTIONS]                                                                                                                                                
                                                                                                                                                                               
 Select segments from a PDB or MMCIF structure file.                                                                                                                           
                                                                                                                                                                               
╭─ Options ───────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────╮
│ *  --input        -I      <path>  Input PDB or MMCIF file [required]                                                                                                        │
│    --output       -O      <path>  Output PDB file, defaults to <input stem>_selected.pdb in the current working directory                                                   │
│ *  --segment      -S      <str>   Segments to select, either 'chain' (whole chain, e.g. A) or 'chain:start-end' (e.g. A:1-10). Repeatable. The start-end range filters      │
│                                   polymer residues only; HETATM residues on the same chain are gated solely by --keep-hetero.                                               │
│                                   [required]                                                                                                                                │
│    --keep-hetero  -H      <str>   Keep HETATM residues. Repeatable. Each entry is 'spec' where spec is 'none','all', or a comma-separated list of residue names (e.g. 'ZN'  │
│                                   or 'ZN,HOH'). An entry without a colon/chain is the global default for every chain; an entry with a chain (e.g. 'A:all') overrides the    │
│                                   global set for that chain. Entries in the same scope are combined by union (-H ZN -H HOH == -H ZN,HOH); a chain entry replaces, not       │
│                                   merges with, the global set. A chain must also appear in --segment, otherwise it is dropped before -H is consulted.                       │
│    --help                         Show this message and exit.                                                                                                               │
╰─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────╯

example:

pdb-md select -I znf263_all_hs7_30_0.54_0.37_model_0.cif -O znf263_all_hs7_30_0.54_0.37_model_0_selected.pdb -S A:369-683 -S B -S C -S D -S E -S F -S G -S H -S I -S J -S K:1-47 -S L:29-75 -H ZN

change from to

Selecting HETATM / heterogen residues

In short: polymer residue is governed by range + chain double filter, while HETATM is governed by chain only. The --keep-hetero option is the only way to keep HETATM residues.

HETATM residues (ions, ligands, waters, sugars) are selected at the chain level, not by residue range. The chain:start-end syntax filters polymer residues only.

Consequences:

• A chain made entirely of HETATM (e.g. a single Zn ion, a glycan chain) is governed by the chain whitelist alone — -S B keeps the whole Zn.
• On a mixed chain, chain:start-end does NOT narrow which HETATM are kept: -S A:1-3 --keep-hetero UNX still keeps UNX at resid 109, because the HETATM branch ignores regions.
• --keep-hetero '' (default) drops every HETATM; all keeps them all; a comma list (e.g. ZN, HOH) is an exact resname whitelist (case-insensitive).

To pick specific HETATM on a mixed chain, split the chain in preprocessing (e.g. give the heterogen its own chain id) — the current CLI has no per-HETATM range selector.

--keep-hetero syntax

-H is repeatable. Each entry is [chain:]spec:

Two rules govern how entries combine:

1. Union within the same scope. Several entries for the same scope add up: -H ZN -H HOH ≡ -H ZN,HOH, and -H E:ZN -H E:HOH ≡ -H E:ZN,HOH. Adding an entry never removes something already whitelisted.
2. A chain entry overrides the global entry. A chain that has its own [chain:] entry uses only that set and ignores the global one. This is what makes per-chain removal expressible: -H ZN -H J:none keeps ZN everywhere except chain J.

A -H chain id must also appear in --segment; otherwise the chain is dropped before -H is ever consulted, and a warning is printed.

2️⃣ preprocessing for MD simulation

Here we summariz e several important easy to use application for fixing problems in Protein Data Bank files in preparation for simulating them.

normal preprocessing

cited from pdbfixer manual

- If the structure was generated by X-ray crystallography, most or all of the hydrogen atoms will usually be missing.
- There may also be missing heavy atoms in flexible regions that could not be clearly resolved from the electron density. This may include anything from a few atoms at the end of a sidechain to entire loops.
- Many PDB files are also missing terminal atoms that should be present at the ends of chains.
- The file may include nonstandard residues that were added for crystallography purposes, but are not present in the naturally occurring molecule you want to simulate.
- The file may include more than what you want to simulate. For example, there may be salts, ligands, or other molecules that were added for experimental purposes. Or the crystallographic unit cell may contain multiple copies of a protein, but you only want to simulate a single copy.
- There may be multiple locations listed for some atoms.
- If you want to simulate the structure in explicit solvent, you will need to add a water box surrounding it.
- For membrane proteins, you may also need to add a lipid membrane.

you can

Add missing heavy atoms.
Add missing hydrogen atoms.
Build missing loops.
Convert non-standard residues to their standard equivalents.
Select a single position for atoms with multiple alternate positions listed.
Delete unwanted chains from the model.
Delete unwanted heterogens.
Build a water box for explicit solvent simulations.

Remove Chains
Identify Missing Residues
Replace Nonstandard Residues
Remove Heterogens
Add Missing Heavy Atoms
Add Missing Hydrogens
Add Water
Add Membrane

Removal of terminal phosphate group for Nucleic Acid

It is usually suggested that while preparing a nucleic acid system for simulation, 5' terminal phosphate group must be removed; or any terminal charged phosphate group should be removed...

Nucleic acids typically do not have 5’-phosphate groups. Force fields are parametrized to the most common use cases and do not necessarily cover all possible chemical space. Delete the phosphate atoms from the 5’-nucleotide and you can generate the topology such that it has a free 5’-hydroxyl group.

In most cases, e.g. for DNA simulations, 5’-phosphate groups are less cared about, so you can just delete them

Remove any phosphate group from terminal residues; these are often present synthetically but are not how force fields are typically parametrized (5’-OH terminus is typical).

In detail, we just need to remove the [O1P/OP1, O2P/OP2, O3P/OP3 if exists, P, Hydrogens attached to them] atoms from the 5' terminal residue of a nucleic acid chain.

You can use the termini-rm5p command to remove the 5' terminal phosphate group from nucleic acids as talked above.

protonation(add hydrogens)

protonation state of the protein is important for MD simulation. The protonation state of a protein can be determined by the pH of the environment, which can affect the charge and conformation of the protein.

Here we summarize several tools for predicting or assigning the protonation state of a protein:

Basically predicted/assigned based on comparison between Pka calculation and the pH of the environment.

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A typical workflow for preparing a PDB file for MD simulation

pdbfixer