The PharmMapper online tool is a web server for potential drug target identification by reversed pharmacophore matching the query compound against an in-house model database. original version of includes more than 7000 pharmacophores derived from complex crystal structures with corresponding protein annotations. In this article, we present new server, which backend database six times larger earlier one, total 23 236 proteins covering 16 159 druggable models and 51 431 ligandable models....

In silico drug target identification, which includes many distinct algorithms for finding disease genes and proteins, is the first step in discovery pipeline. When 3D structures of targets are available, problem identification usually converted to best interaction mode between potential candidates small molecule probes. Pharmacophore, spatial arrangement features essential a interact with specific receptor, an alternative method achieving this goal apart from molecular docking method....

PharmMapper is a web server for drug target identification by reversed pharmacophore matching the query compound against an annotated model database, which provides computational polypharmacology prediction approach repurposing and side effect risk evaluation. But due to inherent nondiscriminative feature of simple fit scores used results ranking, signal/noise ratio high, posing challenge predictive reliability. In this paper, we improved accuracy generating ligand–target pairwise score...

Abstract Background Target identification is important for modern drug discovery. With the advances in development of molecular docking, potential binding proteins may be discovered by docking a small molecule to repository with three-dimensional (3D) structures. To complete this task, reverse program and target database 3D structures are necessary. end, we have developed web server tool, TarFisDock ( Tar get Fis hing Dock ing) http://www.dddc.ac.cn/tarfisdock , which has been used widely...

We developed a novel approach called SHAFTS (SHApe-FeaTure Similarity) for 3D molecular similarity calculation and ligand-based virtual screening. adopts hybrid metric combined with shape colored (labeled) chemistry groups annotated by pharmacophore features ranking, which is designed to integrate the strength of matching volumetric overlay approaches. A feature triplet hashing method used fast alignment poses enumeration, optimal superposition between target query molecules can be...

Drug-induced hepatotoxicity may cause acute and chronic liver disease, leading to great concern for patient safety. It is also one of the main reasons drug withdrawal from market. Toxicogenomics data has been widely used in prediction. In our study, we proposed a multi-dose computational model predict drug-induced based on gene expression toxicity data. The dose/concentration information after treatment fully utilized study dose-response curve, thus more informative representative...

The phytohormone auxin is essential for plant growth and development, YUCCA (YUC) proteins catalyze a rate-limiting step endogenous biosynthesis. Despite YUC family genes have been isolated from several species, systematic expression analyses of YUCs in response to abiotic stress are lacking, little known about the function homologs agricultural crops. Cucumber (Cucumis sativus L.) world cultivated vegetable crop with great economical nutritional value. In this study, we 10 (CsYUCs) cucumber...

We described a prospective application of ligand-based virtual screening program SHAFTS to discover novel inhibitors for p90 ribosomal S6 protein kinase 2 (RSK2). Taking the putative 3D conformations two weakly binding RSK2 NTKD as query templates, was used perform similarity based because lack crystal structure protein, thus leading identification several scaffolds that would have been missed by conventional 2D fingerprint methods. The most potent hit compounds show low micromolar...

This study aimed to evaluate the performance of deep convolutional neural network (DCNN) discriminate between benign, borderline, and malignant serous ovarian tumors (SOTs) on ultrasound(US) images.This retrospective included 279 pathology-confirmed SOTs US images from 265 patients March 2013 December 2016. Two- three-class classification task based were proposed classify using a DCNN. The 2-class was divided into two subtasks: benign vs. borderline & (task A), B). Five DCNN architectures,...

The SPECS database was screened against falcipain-2 with two different docking methods to identify structurally diverse nonpeptidic inhibitors. Twenty-eight molecules among 81 compounds tested were identified as potential inhibitors of falcipain-2. One the exhibited in vitro activity an IC50 value 2.4 μM. Furthermore, similarity analysis has demonstrated that it is feasible find novel similar steric shape through virtual screening large-scale chemical libraries.

Non-small-cell lung carcinoma (NSCLC) mainly consists of two subtypes: squamous cell (LUSC) and adenocarcinoma (LUAD). It has been reported that the genetic epigenetic profiles vary strikingly between LUAD LUSC in process tumorigenesis development. Efficient precise treatment can be made if subtypes identified correctly. Identification discriminative expression signatures explored recently to aid classification NSCLC subtypes.In this study, we designed a model integrating both mRNA long...

Cancer vaccines generally are limited by insufficient tumor-specific cellular immunogenicity. Herein, a potent "ABC" ternary membrane-derived vaccine system blended from antigen-presenting mature dendritic cell membranes ("A"), bacterial E. coli cytoplasmic ("B"), and cancer ("C") is developed using block-copolymer micelle-enabled approach. The respective ABC membrane components provide for source of immune communication/activation enhanced accumulation in lymph nodes (A), immunological...

Conformation generation is a ubiquitous problem in molecule modelling. Many applications require sampling the broad molecular conformational space or perceiving bioactive conformers to ensure success. Numerous silico methods have been proposed an attempt resolve problem, ranging from deterministic non-deterministic and systemic stochastic ones. In this work, we described efficient conformation method named Cyndi, which based on multi-objective evolution algorithm. The perturbation subjected...

The discovery of HpFabZ inhibitors is now special interest in the treatment various gastric diseases. In this work, three series derivatives (compounds 3, 4, and 5) were designed, synthesized, their biological activities investigated as potential a two phased manner. First, we designed synthesized (3a−r 4a−u) evaluated enzyme-based assay against HpFabZ. Five compounds (3i−k, 3m, 3q) showed inhibitory activity, with IC50 values less than 2 μM. Second, focused combinatorial library containing...

Development of a fast and accurate scoring function in virtual screening remains hot issue current computer-aided drug research. Different functions focus on diverse aspects ligand binding, no single can satisfy the peculiarities each target system. Therefore, idea consensus score strategy was put forward. Integrating several functions, re-assesses docked conformations using primary function. However, it is not really robust efficient from perspective optimization. Furthermore, to date,...

Abstract Background The progress in computer-aided drug design (CADD) approaches over the past decades accelerated early-stage pharmaceutical research. Many powerful standalone tools for CADD have been developed academia. As programs are by various research groups, a consistent user-friendly online graphical working environment, combining computational techniques such as pharmacophore mapping, similarity calculation, scoring, and target identification is needed. Results We presented...

Abstract A fabric hydrogel composite hernia mesh with biomechanical and mesh–tissue interface dual compliance is designed for scarless abdominal wall reconstruction. The composed of a polyester knitted chitosan–polyacrylamide complex. mechanical properties the are adjusted to resemble human by alkali treatment chitosan achieve good compliance. An adhesion group introduced into that forms covalent bonds tissue, eliminating need suturing, reducing stress concentration at fixation site,...

Background Low back pain and lower extremity sensory functional abnormalities are common symptoms of lumbar disc herniation (LDH), which can easily cause walking dysfunction significantly impair the quality life patients. Tuina traditional Chinese exercises (TCEs) effective in relieving restoring dysfunction, both often used China as a combination passive therapy active exercise to ease patients with LDH. However, majority current clinical trials on treatment LDH or TCEs single-centre...

Background Handedness refers to the lateral preference of using one hand more than other. Surgeon handedness has been widely discussed in operative surgery and could cause clinical discrepancy. However, use proximal femoral nail antirotation (PFNA) for treatment intertrochanteric femur fracture (IFF), effect on outcomes is easily overlooked. In fact, when right-handed surgeons operate right-sided IFF patients, due specific nature surgical site, they have their left perform opening at end...

The spatial distribution of proteome at subcellular levels provides clues for protein functions, thus is important to human biology and medicine. Imaging-based methods are one the most approaches predicting location. Although deep neural networks have shown impressive performance in a number imaging tasks, its application localization has not been sufficiently explored. In this study, we developed imaging-based approach localize proteins levels. Based on image features extracted from...

Abstract This study aims to evaluate the impact of percutaneous pedicle screw fixation (PPSF) and open (OPSF) on postoperative paraspinal muscle fat infiltration (FI) rate in patients with thoracolumbar fractures through magnetic resonance imaging (MRI), explore association between FI regional kyphosis angle. We retrospectively analyzed clinical data from 35 who underwent either PPSF or OPSF for fractures, examining at preoperative, 1-month postoperative, 9-months time points, which included...

Abstract Background Conformational sampling for small molecules plays an essential role in drug discovery research pipeline. Based on multi-objective evolution algorithm (MOEA), we have developed a conformational generation method called Cyndi the previous study. In this work, addition to Tripos force field version, was updated by incorporation of MMFF94 assess energy more rationally. With two fields against larger dataset 742 bioactive conformations ligands extracted from PDB, comparative...