A Method for Clustering and Screening of Long-dimensional Chemical Data Based on Fingerprints and Similarity Measurements

A method for the treatment of long-dimensional chemical data arrays is presented in this work with the aim of maximising classification models. The method is based on the construction of fingerprints and the subsequent generation of a similarity matrix. The similarity calculation has been modified through a scaling process to take into account different significance shown by the variables. The method was applied to spectral measurements of wines and several aspects were studied, namely: threshold considered in the construction of fingerprints and patterns, weighting factor used for scaling, normalisation method, etc. The application of both Principal Components Analysis and Soft-Independent Modelling of Class Analogies to the similarity matrices gave better classifications of the information than those obtained using original data.     

A systematic docking approach. Application to the α-cyclodextrin/phenyl-ethanol complex

A new approach for systematic docking is applied to the structure of the -cyclodextrin/phenyl-ethanol complex. This methodology includes systematic scanning of the possible guest positions, clustering of low energy structures into families and final refinement using molecular mechanics. The clustering was performed on internal parameters of the complex by a program named PROXIM based on a very simple proximity criterion. This program organized nearly 30 000 structures into about 100 families. Thirty conformations have been considered (10 and 20 for the complexation on the primary and secondary face respectively), the two forms of complexation encountered in the crystal packing yield the lowest energy combination.     

Identifying the binding mode of a molecular scaffold

We describe a method for docking of a scaffold-based series and present its advantages over docking of individual ligands, for determining the binding mode of a molecular scaffold in a binding site. The method has been applied to eight different scaffolds of protein kinase inhibitors (PKI). A single analog of each of these eight scaffolds was previously crystallized with different protein kinases. We have used FlexX to dock a set of molecules that share the same scaffold, rather than docking a single molecule. The main mode of binding is determined by the mode of binding of the largest cluster among the docked molecules that share a scaffold. Clustering is based on our 'nearest single neighbor' method [J. Chem. Inf. Comput. Sci., 43 (2003) 208-217]. Additional criteria are applied in those cases in which more than one significant binding mode is found. Using the proposed method, most of the crystallographic binding modes of these scaffolds were reconstructed. Alternative modes, that have not been detected yet by experiments, could also be identified. The method was applied to predict the binding mode of an additional molecular scaffold that was not yet reported and the predicted binding mode has been found to be very similar to experimental results for a closely related scaffold. We suggest that this approach be used as a virtual screening tool for scaffold-based design processes.     

Validation of multivariate screening methodology. Case study: Detection of food fraud

Multivariate screening methods are increasingly being implemented but there is no worldwide harmonized criterion for their validation. This study contributes to establish protocols for validating these methodologies. We propose the following strategy: (1) Establish the multivariate classification model and use receiver operating characteristic (ROC) curves to optimize the significance level (α) for setting the model’s boundaries. (2) Evaluate the performance parameter from the contingency table results and performance characteristic curves (PCC curves). The adulteration of hazelnut paste with almond paste and chickpea flour has been used as a case study. Samples were analyzed by infrared (IR) spectroscopy and the multivariate classification technique used was soft independent modeling of class analogies (SIMCA). The ROC study showed that the optimal α value for setting the SIMCA boundaries was 0.03 in both cases. The sensitivity value was 93%, specificity 100% for almond and 98% for chickpea, and efficiency 97% for almond and 93% for chickpea.     

发酵虫草菌粉及产品指纹图谱建立及多指标成分分析

《中国药典》收载的发酵虫草菌粉产品的质量标准中,规定以鸟苷、腺苷、尿苷的含量作为评价相关产品质量的标准.但除此之外,还有许多其他的核苷类成分对发酵虫草菌粉质量控制的影响尚未被探讨.为探究发酵虫草菌粉及产品质控指标选择的合理性,采用超高效液相色谱-紫外检测法对19批发酵虫草菌粉及产品中9种核苷成分(尿嘧啶、胞苷、鸟嘌呤、...     

DSC spectra as thermal fingerprints of percolative microemulsions

Three component percolative W/O microemulsions were studied by differential scanning calorimetry. Water-AOT-Decane, D₂O-AOT-Decane, Water-AOT-Isooctane and Water-Ca(AOT)₂-Decane systems were analyzed. Thus by changing, in the order, the dispersed phase, the dispersing medium, and by modifying the interphase region. The thermal history of the samples was monitored by a suitable thermal program. Following the latter, first order phase transitions associated with the freezing and/or melting of the two massive phases were obtained, as well as the higher order phase transition associated with the percolation process. From the melting spectra an estimate of the amount of water bound to the hydrophilic groups of the AOT as well as of that of oil bound to the hydrophobic surfactant tails was obtained. The latter result shows a difference in the behaviour of the continuous oily phase at the O/W interphase. From the freezing spectra, the percolative character of the microemulsion was evidenced by the exotherms associated with the freezing of the water phase. This work was supported by M.U.R.S. T. and I.N.F.M.     

Deciphering common failures in molecular docking of ligand-protein complexes

Common failures in predicting crystal structures of ligand-protein complexes are investigated for three ligand-protein systems by a combined thermodynamic and kinetic analysis of the binding energy landscapes. Misdocked predictions in ligand-protein docking are classified as `soft' and `hard' failures. While a soft failure arises when the search algorithm is unable to find the global energy minimum corresponding to the crystal structure, a hard failure results from a flaw of the energy function to qualify the crystal structure as the predicted lowest energy conformation in docking simulations. We find that neither the determination of a single structure with the lowest energy nor finding the most common binding mode is sufficient to predict crystal structures of the complexes, which belong to the category of hard failures. In a proposed hierarchical approach, structural similarity clustering of the conformations, generated from equilibrium simulations with the simplified energy function, is followed by energy refinement with the AMBER force field. This protocol, that involves a hierarchy of energy functions, resolves some common failures in ligand-protein docking and detects crystallographic binding modes that were not found during docking simulations.     

磷光碳点粉末的合成及其在抗背景干扰的潜指纹成像中的应用

以乙二胺、磷酸和硼酸为反应物,采用水热法制备了荧光碳点(CDs)溶液,进一步加热水热反应溶液,获得了磷光CDs粉末。利用X射线衍射(XRD)、透射电子显微镜(TEM)、X射线光电子能谱(XPS)、紫外可见(UV-Vis)吸收光谱和光致发光光谱等对CDs的结构、形貌和尺寸、表面基团与化学组成以及光学特性进行了表征。结果表明,合成的CDs粉末为无定型碳,形貌为单分散的近球形,尺寸分布在3.78~7.64 nm范围之内,其表面存在大量的N、P和B杂原子基团。CDs粉末在365 nm紫外光照射下呈现明亮的蓝色荧光,关闭激发光后,呈现长达10 s的绿色室温磷光。该CDs粉末可作为指纹试剂应用于具有复杂背景图案且有强荧光发射基质表面的潜指纹(LFPs)显现。显现后的LFPs在激发光关闭后均呈现明亮完整的磷光指纹图谱,指纹细节特征清晰可辨,有效消除了背景图案与背景荧光干扰。同时,制备的CDs粉末对不同干扰背景客体表面老化7 d的LFPs也能够显现出清晰可识别的磷光指纹图谱。     

磷光碳点粉末的合成及其在抗背景干扰的潜指纹成像中的应用

以乙二胺、磷酸和硼酸为反应物,采用水热法制备了荧光碳点(CDs)溶液,进一步加热水热反应溶液,获得了磷光CDs粉末。利用X射线衍射(XRD)、透射电子显微镜(TEM)、X射线光电子能谱(XPS)、紫外可见(UV-Vis)吸收光谱和光致发光光谱等对CDs的结构、形貌和尺寸、表面基团与化学组成以及光学特性进行了表征。结果表明,合成的CDs粉末为无定型碳,形貌为单分散的近球形,尺寸分布在 3.78~7.64 nm范围之内,其表面存在大量的 N、P和 B杂原子基团。CDs粉末在 365 nm紫外光照射下呈现明亮的蓝色荧光,关闭激发光后,呈现长达10 s的绿色室温磷光。该CDs粉末可作为指纹试剂应用于具有复杂背景图案且有强荧光发射基质表面的潜指纹(LFPs)显现。显现后的LFPs在激发光关闭后均呈现明亮完整的磷光指纹图谱,指纹细节特征清晰可辨,有效消除了背景图案与背景荧光干扰。同时,制备的CDs粉末对不同干扰背景客体表面老化7 d的LFPs也能够显现出清晰可识别的磷光指纹图谱。