Predicting small molecule fluorescent probe localization in living cells using QSAR modeling. 2. Specifying probe, protocol and cell factors; selecting QSAR models; predicting entry and localization
Predicting small molecule fluorescent probe localization in living cells using QSAR modeling. 2. Specifying probe, protocol and cell factors; selecting QSAR models; predicting entry and localization
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DOI：
10.3109/10520295.2013.780635
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发表时间：
2013-11-01
影响因子：
1.6
通讯作者：
Rashid-Doubell, F.
中科院分区：
文献类型：
--
作者：
Horobin, R. W.;Rashid-Doubell, F.
我们描述了实际问题和方法程序，必须进行构建和使用QSAR模型来预测探针在单个细胞中的定位。我们首先讨论探针因子的确定，首先考虑探针分子的化学性质。他们的身份是什么？在培养液中或细胞内是否产生新的化合物？对于每个探针，有多少不同的化学物质存在？对于每个探针种类，以下数值结构参数的推导，或描述符，与电荷和酸碱强度（Z和pKa）的工作示例一起列出；亲水性/亲脂性（log P）；两亲性（AI和HGH）；共轭键数和最大共轭片段（CBN和LCF）；宽度和长度（W和L）；分子量、离子质量、头基大小和取代基体积（MW、IW、HGS和SB）。接下来，通过分别关注探针引入细胞的模式、其他应用现象和直接影响结果观察的因素来指定方案因素。然后通过分别考虑结构和功能方面来指定细胞因子。下一步是选择合适的QSAR模型，并整合探针、方案和细胞因素来预测探针与细胞的相互作用。最后，我们使用一个扩展的案例来探索某些光动力治疗染料的细胞内定位来说明这些过程。
We describe the practical issues and the methodological procedures that must be carried out to construct and use QSAR models for predicting localization of probes in single cells. We address first the determination of probe factors starting with a consideration of the chemical nature of probe molecules present. What is their identity? Do new compounds arise in incubation media or intracellularly? For each probe, how many distinct chemical species are present? For each probe species, the derivation of the following numerical structure parameters, or descriptors, is set out with worked examples of electric charge and acid/base strength (Z and pKa); hydrophilicity/lipophilicity (log P); amphiphilicity (AI and HGH); conjugated bond number and largest conjugated fragment (CBN and LCF); width and length (W and L); and molecular and ionic weights, head group size and substituent bulk (MW, IW, HGS and SB). Next, protocol factors are specified by focusing separately on the mode of introduction of the probe to the cells, other application phenomena, and factors that influence directly observations of outcomes. Cell factors then are specified by considering separately structural and functional aspects. The next step is to select appropriate QSAR models and to integrate probe, protocol and cell factors to predict the interactions of the probe with the cell. Finally, we use an extended case example to explore the intracellular localization of certain photodynamic therapy dyes to illustrate these procedures.