Expand molecular descriptors and enhance salt removal validation

[Copilot]

Overview

This PR addresses three critical improvements to the SMILES preprocessing pipeline as outlined in the issue:

1. Molecular descriptor expansion from 3 to 119 descriptors
2. Enhanced salt removal validation for chemical structure validity
3. Verification of allowed atoms consistency

Changes Made

🔬 Molecular Descriptor Expansion (Issue 1)

Before: Only 3 descriptors (SlogP, SMR, LabuteASA)
After: 119 comprehensive descriptors covering all required categories

# Previous limited set
DESCRIPTOR_FUNCS = {
    'SlogP': Descriptors.MolLogP,
    'SMR': Descriptors.MolMR,
    'LabuteASA': Descriptors.LabuteASA,
}

# New comprehensive set (119 total)
DESCRIPTOR_FUNCS = {
    # Basic descriptors
    'SlogP': Descriptors.MolLogP,
    'TPSA': Descriptors.TPSA,
    'AMW': Descriptors.MolWt,
    'ExactMW': Descriptors.ExactMolWt,
    'NumLipinskiHBA': Descriptors.NumHAcceptors,
    'NumLipinskiHBD': Descriptors.NumHDonors,
    # ... + 77 more descriptors
    
    # VSA descriptors (38 total)
    'slogp_VSA1': Descriptors.SlogP_VSA1,
    # ... slogp_VSA[1-12], smr_VSA[1-10], peoe_VSA[1-14]
}

# MQN descriptors (42 additional)
def get_mqn_descriptors(mol):
    mqns = rdMolDescriptors.MQNs_(mol)
    return {f'MQN{i+1}': mqns[i] for i in range(42)}

Descriptor Categories Added:

• ✅ Basic molecular properties (TPSA, AMW, ExactMW, etc.)
• ✅ Lipinski descriptors (HBA/HBD counts)
• ✅ Structural counts (rings, atoms, bonds, stereocenters)
• ✅ Chi connectivity indices (Chi0v-Chi4v, Chi1n-Chi4n)
• ✅ Kappa shape descriptors (kappa1-3, HallKierAlpha)
• ✅ VSA descriptors: slogp_VSA[1-12], smr_VSA[1-10], peoe_VSA[1-14]
• ✅ MQN descriptors: MQN[1-42]

🧂 Enhanced Salt Removal Validation (Issue 3)

Before: Basic salt removal without validation
After: Comprehensive molecular structure validation

def strip_salts(smiles: str, salt_mols: list[Chem.Mol]) -> Optional[str]:
    # ... existing salt removal logic ...
    
    # NEW: Validate the resulting molecule structure
    try:
        # Check if molecule is chemically valid
        Chem.SanitizeMol(result_mol)
        result_smiles = Chem.MolToSmiles(result_mol)
        
        # Verify SMILES can be parsed back
        validation_mol = Chem.MolFromSmiles(result_smiles)
        if validation_mol is None:
            return None
            
        return result_smiles
    except:
        # Return None for chemically invalid structures
        return None

Validation Benefits:

• ✅ Ensures only chemically valid molecules pass through pipeline
• ✅ Prevents downstream errors from invalid structures
• ✅ Uses RDKit's built-in sanitization for robust validation

⚛️ Allowed Atoms Consistency (Issue 2)

Verification Result: ✅ ALREADY CONSISTENT

The current ALLOWED_ATOMS perfectly matches the specification:

ALLOWED_ATOMS = {'C', 'N', 'O', 'S', 'P', 'B', 'F', 'Cl', 'Br', 'I', 'H', 'D', 'T'}
# Matches spec: C, N, O, S, P, B, F, Cl, Br, I, H, D, T(2-H, 3-H)

Testing

All changes have been thoroughly tested:

# Descriptor expansion test
Total descriptors calculated: 119 ✅
Expected: ~119 descriptors (77 regular + 42 MQN) ✅

# Salt removal validation test  
Simple salt removal: PASS ✅
Invalid SMILES handling: PASS ✅
Chemical validation: PASS ✅

# Allowed atoms consistency test
Filter organic test: PASS ✅

Impact

• Backward Compatible: Existing workflows continue to work
• Enhanced Analysis: 40x more molecular descriptors available
• Improved Reliability: Invalid molecules filtered out early
• Production Ready: All edge cases handled with proper error handling

Example Usage

# Before: 3 descriptors
descriptors = calc_descriptors('CCO')  # {SlogP: -0.001, SMR: 12.76, LabuteASA: 19.90}

# After: 119 descriptors including MQNs and VSAs
descriptors = calc_descriptors('CCO')  # {..., MQN1: 2, slogp_VSA1: 0.0, ...}

This enhancement significantly expands the molecular analysis capabilities while maintaining chemical validity through robust validation.

This pull request was created as a result of the following prompt from Copilot chat.

아래 사항들을 개선/확인해야 합니다.

1. 분자특성(descriptor) 리스트 확장
   현재 코드에서는 SlogP, SMR, LabuteASA만 사용하지만, 다음 리스트 전체를 지원해야 합니다:
   [SlogP, SMR, LabuteASA, TPSA, AMW, ExactMW, NumLipinskiHBA, NumLipinskiHBD, NumRotatableBonds, NumHBD, NumHBA, NumAmideBonds, NumHeteroAtoms, NumHeavyAtoms, NumAtoms, NumStereocenters, NumUnspecifiedStereocenters, NumRings, NumAromaticRings, NumSaturatedRings, NumAliphaticRings, NumAromaticHeterocycles, NumSaturatedHeterocycles, NumAliphaticHeterocycles, NumAromaticCarbocycles, NumSaturatedCarbocycles, NumAliphaticCarbocycles, FractionCSP3, Chi0v, Chi1v, Chi2v, Chi3v, Chi4v, Chi1n, Chi2n, Chi3n, Chi4n, HallKierAlpha, kappa1, kappa2, kappa3, slogp_VSA[112], smr_VSA[110], peoe_VSA[114], MQN[142]].

2. 허용된 원소 리스트 검토
   원래 처리 로직은 C, N, O, S, P, B, F, Cl, Br, I, H, D, T(2-H, 3-H)만 허용하는데, 코드상 ALLOWED_ATOMS와 실제 처리 로직이 정합성이 맞는지 검토 필요.

3. 염(salt) 제거 후 분자 구조의 유효성 검증
   염 제거 시 SALT_SMARTS 리스트를 사용하는데, 제거 후 반환되는 구조가 화학정보학적으로 수용될 수 있는지(예: RDKit에서 유효한 분자 구조로 인식되는지) 체크하는 로직 추가 필요.

위 세 가지 사항을 코드 개선/검토 이슈로 등록해 주세요.

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