3D Molecular Alignment Tool

Description

Build a molecular alignment tool that superimposes molecules in 3D space and calculates structural similarity metrics. The tool should read molecules from files, generate 3D conformations if needed, align them, and report alignment quality metrics.

Requirements

Input Processing

The program should accept two molecular structure files as input:

• Reference molecule (the structure to align to)
• Query molecule (the structure to be aligned)

Support the following input formats:

• SMILES strings (text files with .smi extension)
• MOL block format files (.mol extension)

3D Conformation Handling

If input molecules lack 3D coordinates:

• Generate 3D conformations for molecules that need them
• Optimize the generated conformations using an appropriate force field

Molecular Alignment

Perform 3D structural alignment:

• Align the query molecule to the reference molecule
• Use all heavy atoms for the alignment calculation
• Preserve the original reference molecule coordinates

Output Metrics

Calculate and report the following alignment metrics:

• RMSD (Root Mean Square Deviation) between the aligned structures
• A binary indicator (true/false) of whether the alignment is considered "good" (RMSD < 2.0 Angstroms)

Output File

Write the aligned query molecule to an output file:

• Save as MOL format (.mol file)
• Include 3D coordinates of the aligned conformation
• Name the output file aligned_query.mol

Test Cases

Test Case 1: Simple Aromatic Alignment { @test }

Input:

• Reference molecule (reference.smi): c1ccccc1 (benzene)
• Query molecule (query.smi): c1ccc(O)cc1 (phenol)

Expected behavior:

• Both molecules should have 3D conformations generated
• Query molecule should align to reference
• RMSD should be calculated and reported
• Aligned structure saved to aligned_query.mol
• The "good alignment" indicator should be printed

Test Case 2: Pre-existing 3D Coordinates { @test }

Input:

• Reference molecule with 3D coordinates (reference.mol): pre-generated MOL file
• Query molecule with 3D coordinates (query.mol): pre-generated MOL file

Expected behavior:

• Molecules should be aligned using existing coordinates
• RMSD should be calculated and reported
• Aligned structure saved to aligned_query.mol

Test Case 3: Alignment Quality Assessment { @test }

Input:

• Reference molecule (reference.smi): CCO (ethanol)
• Query molecule (query.smi): c1ccccc1 (benzene)

Expected behavior:

• Both molecules should have 3D conformations generated
• Alignment should be performed
• RMSD should be calculated
• The "good alignment" indicator should likely be false (dissimilar structures)
• Aligned structure saved to aligned_query.mol

Dependencies { .dependencies }

rdkit { .dependency }

Provides cheminformatics capabilities for molecular manipulation, 3D structure generation, and alignment operations.