分子基础操作与药效团查找
文章目录
- 1.原子操作
- 2.键操作
- 3.环操作
- 4.手动实现氧族药效团查找
1.原子操作
在rdkit中，分子中的每一个原子都是对象，可以通过原子对象的属性和函数来获取各种信息。
- 对原子进行遍历：m.GetAtoms()
- 获取原子索引：GetIdx()
- 获取原子序号：GetAtomicNum()
- 获取原子符号：GetSymbol()
- 获取原子连接数（受H是否隐藏影响）：GetDegree()
- 获取原子总连接数（与H是否隐藏无关）：GetTotalDegree()
- 获取原子形式电荷：GetFormalCharge()
- 获取原子杂化方式：GetHybridization()
- 获取原子显式化合价：GetExplicitValence()
- 获取原子隐式化合价：GetImplicitValence()
- 获取原子总的化合价：GetTotalValence()
- ...
>>> from rdkit import Chem
>>> m = Chem.MolFromSmiles('C1OC1')
>>> print('\t'.join(['id', 'num', 'symbol', 'degree', 'charge', 'hybrid']))
>>> for atom in m.GetAtoms():
>>> print(atom.GetIdx(), end='\t')
>>> print(atom.GetAtomicNum(), end='\t')
>>> print(atom.GetSymbol(), end='\t')
>>> print(atom.GetDegree(), end='\t')
>>> print(atom.GetFormalCharge(), end='\t')
>>> print(atom.GetHybridization())
id num symbol degree charge hybrid
0 6 C 2 0 SP3
1 8 O 2 0 SP3
2 6 C 2 0 SP3
- 也可以通过索引获取原子：GetAtomWithIdx()
>>> print(m.GetAtomWithIdx(0).GetSymbol())
C
- 获取相连的原子：GetNeighbors()
>>> atom = m.GetAtomWithIdx(1)
>>> [x.GetAtomicNum() for x in atom.GetNeighbors()]
[6, 6]
2.键操作
同样，每一个键也都是对象，可以通过属性和函数来获取键的信息。
- 对键进行遍历：m.GetBonds()
- 获取键的索引：GetIdx()
- 获取键的类型：GetGetBondType()
- 以数字形式显示键的类型：GetBondTypeAsDouble()
- 是否为芳香键：GetIsAromatic()
- 是否为共轭键：GetIsConjugated()
- 是否在环中：IsInRing()
- 是否在n元环中：IsInRingSize(n)
- 获取起始原子：GetBeginAtom()
- 获取末尾原子：GetEndAtom()
- ...
>>> m = Chem.MolFromSmiles('C=C-C=C')
>>> print('\t'.join(['id', 'type', 'double', 'aromic', 'conjug', 'ring', 'begin', 'end']))
>>> for bond in m.GetBonds():
>>> print(bond.GetIdx(), end='\t')
>>> print(bond.GetBondType(), end='\t')
>>> print(bond.GetBondTypeAsDouble(), end='\t')
>>> print(bond.GetIsAromatic(), end='\t')
>>> print(bond.GetIsConjugated(), end='\t')
>>> print(bond.IsInRing(), end='\t')
>>> print(bond.GetBeginAtomIdx(), end='\t')
>>> print(bond.GetEndAtomIdx())
id type double aromic conjug ring begin end
0 DOUBLE 2.0 False True False 0 1
1 SINGLE 1.0 False True False 1 2
2 DOUBLE 2.0 False True False 2 3
- 也可以通过索引获取键：GetBondWithIdx()
>>> print(m.GetBondWithIdx(0).GetBondType())
DOUBLE
3.环操作
- 查看原子的环信息
>>> m = Chem.MolFromSmiles('OC1C2C1CC2')
>>> print(m.GetAtomWithIdx(0).IsInRing())
False
>>> print(m.GetAtomWithIdx(2).IsInRing())
True
>>> print(m.GetAtomWithIdx(2).IsInRingSize(3))
True
>>> m
atom_bond_ring_1.png
- 但是要注意，IsInRingSize()函数只能判断是否在最小的环中
>>> print(m.GetAtomWithIdx(2).IsInRingSize(3))
True
>>> print(m.GetAtomWithIdx(2).IsInRingSize(5))
False
- 可以查看所有最小环(smallest set of smallest rings, SSSR）的信息：GetSymmSSSR()
>>> ssr = Chem.GetSymmSSSR(m)
>>> print(len(ssr))
>>> print(list(ssr[0]))
>>> print(list(ssr[1]))
2
[1, 2, 3]
[4, 5, 2, 3]
- 直接获取环的信息：GetRingInfo()
- 查看一共有几个环：NumRings()
- 查看原子在几个环中：NumAtomRings()
- 查看id为n的原子是否在n1元环中.IsAtomInRingOfSize(n, n1)
- 查看id为n的键是否在n1元环中.IsAtomInRingOfSize(n , n1)
>>> ri = m.GetRingInfo()
>>> print(ri.NumRings())
2
>>> print(ri.NumAtomRings(6))
0
>>> print(ri.IsAtomInRingOfSize(1,3))
True
>>> print(ri.IsBondInRingOfSize(1,3))
True
4.手动实现氧族药效团查找
这里只做一个简单的演示，通过原子属性查找目标药效团，更复杂的操作类似。
- 假设要查找的氧族氢供体标准：氧或硫原子，不带电荷，含有1个氢。
- 氧族氢受体标准（部分）：不带氢原子，化合价为2，且不与氮原子相连。
>>> def pharmacophore(m):
>>> atomPharma = {}
>>> # 定义氧族原子
>>> chalcogen = [8, 16]
>>> mol = Chem.MolFromSmiles(m)
>>> mol = Chem.AddHs(mol)
>>> # 开始查找
>>> for atom in mol.GetAtoms():
>>> p = []
>>> if atom.GetAtomicNum() == 1 or atom.GetAtomicNum() not in chalcogen:
>>> continue
>>> else:
>>> # 氢供体
>>> if atom.GetFormalCharge() == 0:
>>> nbrs = [x for x in atom.GetNeighbors()]
>>> HDflag = False
>>> for nbr in nbrs:
>>> if nbr.GetAtomicNum() == 1:
>>> HDflag = True
>>> if HDflag:
>>> p.append('HDonor')
>>> # 氢受体
>>> if atom.GetTotalValence() == 2:
>>> nbrs = [x for x in atom.GetNeighbors()]
>>> HAflag_1 = True
>>> HAflag_2 = True
>>> if len(nbrs) == 1:
>>> nbr = nbrs[0]
>>> if nbr.GetAtomicNum() == 7:
>>> HAflag_1 = False
>>> else:
>>> for nbr in nbrs:
>>> if nbr.GetAtomicNum() == 1:
>>> HAflag_2 = False
>>> if HAflag_1 and HAflag_2:
>>> p.append('HAcceptor')
>>> atomPharma[atom.GetIdx()] = [atom.GetAtomicNum(), ' '.join(p)]
>>> return atomPharma
>>>
>>> m = 'COC(=O)O'
>>> res = pharmacophore(m)
>>> res
{1: [8, 'HAcceptor'], 3: [8, 'HAcceptor'], 4: [8, 'HDonor']}
更简单的操作，直接写成SMARTS查找就可以了
- 氢供体：[O,S;H1;+0]
- 氢受体（部分）：[O;H0;v2;!$(O=N-*)]
>>> def pharmacophore_smarts(m):
>>> # 定义smarts
>>> HDonorSmarts = '[O,S;H1;+0]'
>>> HAcceptorSmarts = '[O;H0;v2;!$(O=N-*)]'
>>> HDonor = Chem.MolFromSmarts(HDonorSmarts)
>>> HAcceptor = Chem.MolFromSmarts(HAcceptorSmarts)
>>> atomPharma = {}
>>> mol = Chem.MolFromSmiles(m)
>>> # 氢供体
>>> HDonors = mol.GetSubstructMatches(HDonor)
>>> for i in HDonors:
>>> atom = mol.GetAtomWithIdx(i[0])
>>> atomPharma[atom.GetIdx()] = [atom.GetAtomicNum(), 'HDonor']
>>> # 氢受体
>>> HAcceptors = mol.GetSubstructMatches(HAcceptor)
>>> for i in HAcceptors:
>>> atom = mol.GetAtomWithIdx(i[0])
>>> atom_prop = atomPharma.get(atom.GetIdx(), [])
>>> if atom_prop:
>>> atom_prop[1] = atom_prop[1] + ' HAcceptor'
>>> atomPharma.update({atom.GetIdx():atom_prop})
>>> else:
>>> atomPharma[atom.GetIdx()] = [atom.GetAtomicNum(), 'HAcceptor']
>>> return atomPharma
>>>
>>> res = pharmacophore_smarts(m)
>>> res
{4: [8, 'HDonor'], 1: [8, 'HAcceptor'], 3: [8, 'HAcceptor']}
