Prediction of blood-brain partitioning using Monte Carlo simulations of molecules in water
Prediction of blood-brain partitioning using Monte Carlo simulations of molecules in water
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DOI：
10.1023/a:1012240703377
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发表时间：
2001-08-01
影响因子：
3.5
通讯作者：
Blankley, CJ
中科院分区：
文献类型：
--
作者：
Kaznessis, YN;Snow, ME;Blankley, CJ
脑血分配系数（log BB）是中枢神经系统作用药物疗效的决定因素。由于对 BB 的大规模实验测定是不可行的，因此基于理论模型的替代评估方法是可取的。朝着这个方向，我们提出了一个模型，将 76 个结构不同的分子的 log BB 与物理上重要的描述符相关联。我们对水中的化合物进行蒙特卡罗模拟，计算溶剂可及表面积 (SASA)、氢键供体和受体的数量、溶质偶极子以及 SASA 的亲水性、疏水性和两亲性成分等特性。识别物理上重要的描述符并构建定量结构预测关系来预测 log BB。这项工作表明，可以在半经验框架中采用计算机模拟来构建预测性 QSPR，从而揭示生物分子现象的物理机制。
The brain-blood partition coefficient (log BB) is a determining factor for the efficacy of central nervous system acting drugs. Since large-scale experimental determination of log BB is unfeasible, alternative evaluation methods based on theoretical models are desirable. Toward this direction, we propose a model that correlates log BB with physically significant descriptors for 76 structurally diverse molecules. We employ Monte Carlo simulations of the compounds in water to calculate such properties as the solvent-accessible surface area (SASA), the number of hydrogen bond donors and acceptors, the solute dipole, and the hydrophilic, hydrophobic and amphiphilic components of SASA. The physically significant descriptors are identified and a quantitative structure-prediction relationship is constructed that predicts log BB. This work demonstrates that computer simulations can be employed in a semi-empirical framework to build predictive QSPRs that shed light on the physical mechanism of biomolecular phenomena.