Structural Surgery: In-memory Mutagenesis

Task: Mutate a residue in a protein and automatically fix the local structural errors (clashes and missing atoms).

Preparing mutants is a common task in rational design. This recipe shows how to perform a mutation and repair the side-chains in a single step.

import molsysmt as msm
from molsysmt import systems

# Load the T4 Lysozyme
lysozyme = systems['T4 lysozyme L99A']['181l.bcif.gz']
molsys = msm.convert(lysozyme, to_form='molsysmt.MolSys')

1. Perform the Mutation

We mutate the Lysine at index 18 to an Alanine. MolSysMT will handle the topological change.

mutated_system = msm.build.mutate(molsys, selection='group_index==18', 
                                  to_group='ALA')

msm.info(mutated_system, element='group', selection=18)

2. Auto-Repair

After a mutation, some atoms might be missing or in poor positions. We use the build module to refine the local environment. A mutation can also change bonds, covalent components, formal charge, aromaticity, implicit hydrogens, or stereochemistry. Treat those values as chemical-state information and verify them after rebuilding instead of assuming the original state is still valid. When reactant and product structures coexist in one MolSys, assign their nullable structure_chemical_state_index values and use chemical_state='structure' with get(), set(), has_attribute(), and select(). This prevents an accidental global reference from being mistaken for per-frame chemical evidence.

final_system = msm.build.add_missing_heavy_atoms(mutated_system)
print("System mutated and repaired successfully.")