Let's not forget tautomers.
Let's not forget tautomers.
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DOI：
10.1007/s10822-009-9303-2
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发表时间：
2009-10
影响因子：
3.5
通讯作者：
Martin, Yvonne Connolly
中科院分区：
文献类型：
--
作者：
Martin, Yvonne Connolly
如果一个化合物可以由两个结构表示，并且这两个结构通过氢从一个原子到另一个原子的分子内运动而相关，则该化合物表现出互变异构现象。分子的不同互变异构体通常具有不同的分子指纹、疏水性和pKa以及不同的3D形状和静电性质;此外，蛋白质经常优先结合在水中以低丰度存在的互变异构体。因此，正确处理可互变异构的分子（约占数据库的25%）对计算机辅助分子设计的各个方面都是一个挑战。专注于分子相似性或多样性的文库设计可能会无意中包括碰巧编码为不同互变异构体的相似分子。物理性质测量可能无法建立个别互变异构体的性质，结果是基于这些测量的算法对于可以互变异构的分子可能不太准确，这个问题影响了库设计和传统QSAR的过滤精度。任何2D或3D QSAR分析必须涉及是否或如何调整观察到的互变异构平衡的Ki或IC 50的决定。定量构效关系和递归分割方法还涉及决定使用哪种互变异构体来计算分子描述符。对接虚拟筛选必须涉及关于在对接中包括哪些互变异构体以及如何在评分中考虑互变异构化的决定。所有这些决定是更困难的，因为没有广泛的数据库中测量的互变异构体的比例在水和非水溶剂，也没有共识的最佳计算方法来计算在不同的环境中的互变异构体的比例。
A compound exhibits tautomerism if it can be represented by two structures that are related by an intramolecular movement of hydrogen from one atom to another. The different tautomers of a molecule usually have different molecular fingerprints, hydrophobicities and pKa’s as well as different 3D shape and electrostatic properties; additionally, proteins frequently preferentially bind a tautomer that is present in low abundance in water. As a result, the proper treatment of molecules that can tautomerize, ~25% of a database, is a challenge for every aspect of computer-aided molecular design. Library design that focuses on molecular similarity or diversity might inadvertently include similar molecules that happen to be encoded as different tautomers. Physical property measurements might not establish the properties of individual tautomers with the result that algorithms based on these measurements may be less accurate for molecules that can tautomerize—this problem influences the accuracy of filtering for library design and also traditional QSAR. Any 2D or 3D QSAR analysis must involve the decision of if or how to adjust the observed Ki or IC50 for the tautomerization equilibria. QSARs and recursive partitioning methods also involve the decision as to which tautomer(s) to use to calculate the molecular descriptors. Docking virtual screening must involve the decision as to which tautomers to include in the docking and how to account for tautomerization in the scoring. All of these decisions are more difficult because there is no extensive database of measured tautomeric ratios in both water and non-aqueous solvents and there is no consensus as to the best computational method to calculate tautomeric ratios in different environments.
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影响因子：
2.8
作者：
Danilov, VI;Stewart, JJP;Alderfer, JL
通讯作者：
Alderfer, JL
DOI：
10.1021/ci60006a016
发表时间：
1976-01-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
--
作者：
DITTMAR, PG;STOBAUGH, RE;WATSON, CE
通讯作者：
WATSON, CE
影响因子：
3.8
作者：
Duarte, HA;Carvalho, S;Simas, AM
通讯作者：
Simas, AM
影响因子：
3
作者：
Garcia-Viloca, M;Alhambra, C;Gao, JL
通讯作者：
Gao, JL
影响因子：
4.9
作者：
Hart, JC;Burton, NA;Jewsbury, P
通讯作者：
Jewsbury, P