Octanol-water partition coefficient measurements for the SAMPL6 blind prediction challenge
Octanol-water partition coefficient measurements for the SAMPL6 blind prediction challenge
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DOI：
10.1007/s10822-019-00271-3
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发表时间：
2020-04-01
影响因子：
3.5
通讯作者：
Chodera, John D.
中科院分区：
文献类型：
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作者：
Isik, Mehtap;Levorse, Dorothy;Chodera, John D.
分配系数描述了一种溶质在两个接触的液相（通常是中性溶质）之间的平衡分配。辛醇-水分配系数（Kowor 它们的对数 (log P)）在药物发现中经常用作亲脂性的度量。分配系数是一种物理化学性质，可捕获水相和非极性相之间相对溶剂化的热力学，因此为基于物理的计算模型提供了极好的测试，该模型可预测药物相关性的性质，例如蛋白质-配体结合亲和力或水合/溶剂化自由能。SAMPL6 第 II 部分辛醇-水分配系数预测挑战在盲实验基准中使用了 SAMPL6 pKa 预测挑战中的激酶抑制剂片段样化合物的子集，直到从参与的计算化学小组收集了所有预测为止，本文介绍了该 SAMPL6 第 II 部分分配系数挑战的辛醇-水 log P 数据集，其中包含 11 种化合物（6 种化合物）。 4-氨基喹唑啉、两种苯并咪唑、一种吡唑并[3,4-d]嘧啶、一种吡啶、一种含有2-氧代喹啉子结构的化合物），log P 值在 1.95-4.09 范围内。
Partition coefficients describe the equilibrium partitioning of a single, defined charge state of a solute between two liquid phases in contact, typically a neutral solute. Octanol-water partition coefficients (Kowor their logarithms (log P), are frequently used as a measure of lipophilicity in drug discovery. The partition coefficient is a physicochemical property that captures the thermodynamics of relative solvation between aqueous and nonpolar phases, and therefore provides an excellent test for physics-based computational models that predict properties of pharmaceutical relevance such as protein-ligand binding affinities or hydration/solvation free energies. The SAMPL6 Part II octanol-water partition coefficient prediction challenge used a subset of kinase inhibitor fragment-like compounds from the SAMPL6 pKa prediction challenge in a blind experimental benchmark. Following experimental data collection, the partition coefficient dataset was kept blinded until all predictions were collected from participating computational chemistry groups. A total of 91 submissions were received from 27 participating research groups. This paper presents the octanol-water log P dataset for this SAMPL6 Part II partition coefficient challenge, which consisted of 11 compounds (six 4-aminoquinazolines, two benzimidazole, one pyrazolo[3,4-d]pyrimidine, one pyridine, one 2-oxoquinoline substructure containing compounds) with log P values in the range of 1.95-4.09. We describe the potentiometric log P measurement protocol used to collect this dataset using a Sirius T3, discuss the limitations of this experimental approach, and share suggestions for future log P data collection efforts for the evaluation of computational methods.