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Structure-based screening using fully flexible docking is still too slow for large molecular libraries. High quality docking of a million molecule library can take days even on a cluster with hundreds of CPUs. This performance issue prohibits the use of fully flexible docking in the design of large combinatorial libraries. We have developed a fast(More)
The preponderance of evidence implicates protein misfolding in many unrelated human diseases. In all cases, normal correctly folded proteins transform from their proper native structure into an abnormal beta-rich structure known as amyloid fibril. Here we introduce a computational algorithm to detect nonnative (hidden) sequence propensity for amyloid fibril(More)
Motivation: Numerous methods for predicting β-turns in proteins have been developed based on various computational schemes. Here, we introduce a new method of β-turn prediction that uses the support vector machine (SVM) algorithm together with predicted secondary structure information. Various parameters from the SVM have been adjusted to achieve optimal(More)
Cancer stem-like cells (CSLCs) contribute to the initiation and recurrence of tumors and to their resistance to conventional therapies. In this study, small interfering RNA (siRNA)-based screening of ∼4800 druggable genes in 3-dimensional CSLC cultures in comparison to 2-dimensional bulk cultures of U87 glioma cells revealed 3 groups of genes essential for(More)
Docking and scoring are critical issues in virtual drug screening methods. Fast and reliable methods are required for the prediction of binding affinity especially when applied to a large library of compounds. The implementation of receptor flexibility and refinement of scoring functions for this purpose are extremely challenging in terms of computational(More)
The calculation of contact-dependent secondary structure propensity (CSSP) is a unique and sensitive method that detects non-native secondary structure propensities in protein sequences. This method has applications in predicting local conformational change, which typically is observed in core sequences of protein aggregation and amyloid fibril formation.(More)
A systematic understanding of genotype-specific sensitivity or resistance to anticancer agents is required to provide improved patient therapy. The availability of an expansive panel of annotated cancer cell lines enables comparative surveys of associations between genotypes and compounds of various target classes. Thus, one can better predict the optimal(More)
LY6K is a cancer biomarker and a therapeutic target that induces invasion and metastasis. However, the molecular mechanisms that determine human LY6K transcription are completely unknown. To elucidate the mechanisms involved in human LY6K gene regulation and expression, multiple cis-elements were predicted using TRANSFAC software, and the LY6K regulatory(More)
Receptor flexibility is a critical issue in structure-based virtual screening methods. Although a multiple-receptor conformation docking is an efficient way to account for receptor flexibility, it is still too slow for large molecular libraries. It was reported that a fast ligand-centric, shape-based virtual screening was more consistent for hit enrichment(More)
We found that a natural product, Sanguinarine, directly interacts with AMPK and enhances its enzymatic activity. Cell-based assays confirmed that cellular AMPK and the downstream acetyl-CoA carboxylase (ACC) were phosphorylated after Sanguinarine treatment. Sanguinarine was shown to exclusively activate AMPK holoenzymes containing α1γ1 complexes, and it(More)