LINGO, an efficient holographic text based method to calculate biophysical properties and intermolecular similarities

SMILES strings are the most compact text based molecular representations. Implicitly they contain the information needed to compute all kinds of molecular structures and, thus, molecular properties derived from these structures. We show that this implicit information can be accessed directly at SMILES string level without the need to apply explicit time-consuming conversion of the SMILES strings into molecular graphs or 3D structures with subsequent 2D or 3D QSPR calculations. Our method is based on the fragmentation of SMILES strings into overlapping substrings of a defined size that we call LINGOs. The integral set of LINGOs derived from a given SMILES string, the LINGO profile, is a hologram of the SMILES representation of the molecule described. LINGO profiles provide input for QSPR models and the calculation of intermolecular similarities at very low computational cost. The octanol/water partition coefficient (LlogP) QSPR model achieved a correlation coefficient R2=0.93, a root-mean-square error RRMS=0.49 log units, a goodness of prediction correlation coefficient Q2=0.89 and a QRMS=0.61 log units. The intrinsic aqueous solubility (LlogS) QSPR model achieved correlation coefficient values of R2=0.91, Q2=0.82, and RRMS=0.60 and QRMS=0.89 log units. Integral Tanimoto coefficients computed from LINGO profiles provided sharp discrimination between random and bioisoster pairs extracted from Accelrys Bioster Database. Average similarities (LINGOsim) were 0.07 for the random pairs and 0.36 for the bioisosteric pairs.     

甲基烷烃结构与色谱保留指数相关性的拓扑指数法研究

计算了207个甲基烷烃的127个拓扑指数变量,把变量选择方法GAPLS方法引入到定量结构与气相色谱保留关系研究中,对127个拓扑指数变量进行选择,得到了含7个变量的化合物的定量结构与色谱保留指数关系(QSRR)模型,其复相关系数的平方为0.99998,标准偏差为2.88。交互验证的复相关系数为0.99997,交互验证的预测标准偏差为2.95,表明该模型具有良好的稳定性和可靠性。对获得的7个变量进行了合理的结构解释,表明甲基烷烃色谱保留指数完全能用拓扑指数来精确表征。     

QSRR Study on the Relationship between the Chromatographic Capacity Factor and Lipophilicity and Structure Parameters of Halogenated Thiophenols

The capacity factors (k') of fourteen types of halogenated thiophenols in different phases of methanol-water eluent were determined by reversed phased high-performance liquid chromatography (RP-HPLC) and the relationships between the logarithm of capacity factor lgK' and methanol ratio ψ were analyzed. A fair linear relationship is found between lgK' and ψ, and the correlation coefficients R2 of the constructed linear equations are all greater than 0.990. Relationship between the chromatographic data lgKw' when extrapolated to pure water and n-octanol/water partition coefficient lgKow obtained by the group contribution method has shown a good linear correlation with R2 = 0.956. The structure parameters of fourteen halogenated thiophenols were calculated by using DFT, and the correlation equation of lgKw' and structure parameters was obtained by using SPSS, lgKw' = -0.409 + 0.039α and R2 = 0.981, meaning that lgKw' is mainly determined by the polarizability α.