Hydrophobic Molecular Similarity from MST Fractional Contributions to the Octanol/water Partition Coefficient

Summary The use of a recently proposed hydrophobic similarity index for the alignment of molecules and the prediction of their differences in biological activity is described. The hydrophobic similarity index exploits atomic contributions to the octanol/water transfer free energy, which are evaluated by means of the fractional partitioning scheme developed within the framework of the Miertus-Scrocco-Tomasi continuum model. Those contributions are used to define global and local measures of hydrophobic similarity. The suitability of this computational strategy is examined for two series of compounds (ACAT inhibitors and 5-HT₃ receptor agonists), which are aligned to maximize the global hydrophobic similarity using a Monte Carlo-simulated protocol. Indeed, the concept of local hydrophobic similarity is used to explore structure–activity relationships in a series of COX-2 inhibitors. Inspection of the 3D distribution of hydrophobic/hydrophilic contributions in the aligned molecules is valuable to identify regions of very similar hydrophobicity, which can define pharmacophoric recognition patterns. Moreover, low similar regions permit to identify structural elements that modulate the differences in activity between molecules. Finally, the quantitative relationships found between the pharmacological activity and the hydrophobic similarity index points out that not only the global hydrophobicity, but its 3D distribution, is important to gain insight into the activity of molecules. J.M.M. and S.P. have contributed equally to this study.     

Design criteria for molecular mimics of fragments of the β-turn. 1. Cα atom analysis

Peptides represent an extensive class of biologically active molecules. They may be used as leads in the development of novel therapeutic agents provided the pharmacophoric information present within them can be translated into non-peptide analogs that lack the peptide backbone and are stable to proteolysis. This is the rationale for peptidomimetic drug design. Frequently, the -turn has been implicated as a conformation important for biological recognition of peptides. Empirical evidence from known peptidomimetics, coupled with a theoretical model of peptide binding and the observation that glycine and proline residues are common within the -turn, has suggested the design of molecules to mimic placement of between two and four of the side-chains. The moderate number of different -turn conformations, combined with the combinatoric nature of side-chain selection complicates the procedure. In this paper, cluster analysis has been used to classify the arrangement of C_{_} atoms about the various fragments of the -turn. Recombination of the observed patterns provides a general model for the -turn which may be used as an effective screen for potential peptidomimetic scaffolds in chemical databases.     

A study for quality evaluation of Taxilli Herba from different hosts based on fingerprint-activity relationship modeling and multivariate statistical analysis

In this study, a fingerprint-activity relationship modeling between chemical fingerprints and antirheumatic activity was established, and multivariate statistical analysis was used to evaluate the quality of Taxilli Herba (TH) from different hosts. Characteristic fingerprints of 20 batches of TH samples were generated by high-performance liquid chromatography coupled with triple quadrupole-time of flight tandem mass spectrometry (HPLC-Triple TOF-MS/MS), and the similarity analysis was calculated based on thirteen common characteristic peaks by hierarchical clustering analysis (HCA). Subsequently, nine efficacy markers were discovered by combining fingerprints and antirheumatic activity through grey correlation analysis (GCA) and bivariate correlation analysis (BCA). Meanwhile, the content of 5 constituents in 9 markers was determined by high-performance liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (HPLC-QTRAP-MS/MS). The comprehensive quality of TH was assessed using multivariate statistical analysis, including principal components analysis (PCA) and technique for order preference by similarity to ideal solution (TOPSIS). The results showed that a high dose of TH extract could markedly ameliorate arthritis damage compared to other doses, with flavonoids playing an important role in the antirheumatic activity. The comprehensive quality of samples from Morus alba L. (SS) was superior to those from Liquidambar formosana Hance (FXS). The present study will demonstrate the markers associated with efficacy, and provide an applicable strategy for more comprehensive quality control and evaluation of TH.     

Characteristic polynomial theory of two-stage phase shifting algorithms

Two-stage phase shifting algorithms make possible to directly recover the sum or the difference of the optical phase of two different fringe patterns. These algorithms can be built by combining the known phase shifting algorithms in a non-linear way. In this work, we associate a two-dimensional characteristic polynomial to each two-stage phase shifting algorithm. This enables us to qualitatively compare their behaviour against the main systematic error sources, by means of an analysis protocol like that used for phase shifting algorithms. We show that this tool allows to understand the propagation of properties from precursor phase shifting algorithms to new evaluation algorithms built from them. As an experimental application, a wavefront distortion evaluation in differential phase-shifting interferometry is presented.     

Towards full-resolution inline electron holography

With the availability of fast computers, inline electron holography, a technique for reconstructing both amplitude and phase of the electron wave function as scattered by the sample from a set of differently aberrated transmission electron microscopy images, is becoming increasingly quantitative. While focal series reconstruction from transmission electron microscopy images has already been practiced for at least 3 decades, existing approaches can only recover a relatively small band of spatial frequencies. Here I present a reconstruction scheme which is capable of reconstructing the electron wave function for a very large range of spatial frequencies, demonstrating its performance using simulated as well as experimental data.     

Phishing attacks discovery based on HTML layout similarity

Based on the similarity of the layout structure between the phishing sites and real sites,an approach to discover phishing sites was presented.First,the tag with link attribute as a feature was extracted,and then based on the feature,the page tag sequence branch to identify website was extracted,followed by the page layout similarity-HTMLTagAntiPhish,the alignment of page tag sequence tree into the alignment of page tag sequence branches was converted,this converted two-dimention tree structure into one-dimention string structure,and finally through the substitution matrix of bioinfor-matics BLOSUM62 coding,alignment score quickly to improve the phishing sites detection efficiency was computed.A series of simulation experiments show that this approach is feasible and has higher precision and recall rates.     

Fast reused code tracing method based on simhash and inverted index

A novel method for fast and accurately tracing reused code was proposed. Based on simhash and inverted in-dex, the method can fast trace similar functions in massive code. First of all, a code database with three-level inverted in-dex structures was constructed. For the function to be traced, similar code blocks could be found quickly according to simhash value of the code block in the function code. Then the potential similar functions could be fast traced using in-verted index. Finally, really similar functions could be identified by comparing jump relationships of similar code blocks. Further, malware samples containing similar functions could be traced. The experimental results show that the method can quickly identify the functions inserted by compilers and the reused functions based on the code database under the premise of high accuracy and recall rate.     

Three‐unit semicircles curve: A compact 3D graphical representation of DNA sequences based on classifications of nucleotides

A new three‐dimensional graphical representation of DNA sequences, three‐unit semicircles (TUS)‐curve, which maps a given sequence into a dot sequences embedded in three‐unit semicircles, is proposed based on three biclassifications of nucleotides. TUS‐curve has the merit of compactness and could avoid the degeneracy and loss of information. The geometrical center of the curve, which indicates the distribution of base frequencies of the corresponding DNA sequence, is extracted and applied to analyze the similarity of various species. Phylogenetic tree of 11 species based on their first exons of β‐globin genes showed that the TUS‐curve is a powerful tool to get valuable biological information. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

A new SVM-based relevance feedback image retrieval using probabilistic feature and weighted kernel function

Relevance feedback (RF) is an effective approach to bridge the gap between low-level visual features and high-level semantic meanings in content-based image retrieval (CBIR). The support vector machine (SVM) based RF mechanisms have been used in different fields of image retrieval, but they often treat all positive and negative feedback samples equally, which will inevitably degrade the effectiveness of SVM-based RF approaches for CBIR. In fact, positive and negative feedback samples, different positive feedback samples, and different negative feedback samples all always have distinct properties. Moreover, each feedback interaction process is usually tedious and time-consuming because of complex visual features, so if too many times of iteration of feedback are asked, users may be impatient to interact with the CBIR system. To overcome the above limitations, we propose a new SVM-based RF approach using probabilistic feature and weighted kernel function in this paper. Firstly, the probabilistic features of each image are extracted by using principal components analysis (PCA) and the adapted Gaussian mixture models (AGMM) based dimension reduction, and the similarity is computed by employing Kullback–Leibler divergence. Secondly, the positive feedback samples and negative feedback samples are marked, and all feedback samples’ weight values are computed by utilizing the samples-based Relief feature weighting. Finally, the SVM kernel function is modified dynamically according to the feedback samples’ weight values. Extensive simulations on large databases show that the proposed algorithm is significantly more effective than the state-of-the-art approaches.