Abstract Proteolysis-targeting chimeras (PROTACs), which selectively degrade targeted proteins by the ubiquitin-proteasome system, have emerged as a novel therapeutic technology with potential advantages over traditional inhibition strategies. In past few years, this has achieved substantial progress and two PROTACs been advanced into phase I clinical trials. However, is still maturing design of remains great challenge. order to promote rational PROTACs, we present PROTAC-DB, web-based...

The past few years have witnessed enormous progress toward applying machine learning approaches to the development of protein-ligand scoring functions. However, robust performance and wide applicability functions remain a big challenge for increasing success rate docking-based virtual screening. Herein, novel function named RTMScore was developed by introducing tailored residue-based graph representation strategy several transformer layers protein ligand representations, followed mixture...

A large number of protein–protein interactions (PPIs) are mediated by the between proteins and peptide segments binding partners, therefore determination protein–peptide (PpIs) is quite crucial to elucidate important biological processes design peptides or peptidomimetic drugs that can modulate PPIs. Nowadays, as a powerful computation tool, molecular docking has been widely utilized predict structures complexes. However, although programs have available, systematic study on assessment their...

Accurate estimation of the synthetic accessibility small molecules is needed in many phases drug discovery. Several expert-crafted scoring methods and descriptor-based quantitative structure–activity relationship (QSAR) models have been developed for assessment, but their practical applications discovery are still quite limited because relatively low prediction accuracy poor model interpretability. In this study, we proposed a data-driven interpretable framework called GASA (Graph...

Abstract Inhibitors that form covalent bonds with their targets have traditionally been considered highly adventurous due to potential off-target effects and toxicity concerns. However, the clinical validation approval of many inhibitors during past decade, design discovery novel attracted increasing attention. A large amount scattered experimental data for reported, but a resource by integrating information inhibitor is still lacking. In this study, we presented Covalent Inhibitor Database...

Structure-based drug design depends on the detailed knowledge of three-dimensional (3D) structures protein-ligand binding complexes, but accurate prediction ligand-binding poses is still a major challenge for molecular docking due to deficiency scoring functions (SFs) and ignorance protein flexibility upon ligand binding. In this study, based cross-docking dataset dedicatedly constructed from PDBbind database, we developed several XGBoost-trained classifiers discriminate near-native decoys,...

Callicarpins A–D (1–4), possessing an unprecedented A-homoent-clerodane scaffold with a bicyclo[5.4.0]undecane ring system, and callicarpins E–G (5–7), 5/6-fused ent-clerodane diterpenoid skeletons, were isolated from Callicarpaarborea C. integerrim. Their structures elucidated by comprehensive spectroscopic data, X-ray crystal diffraction, chemical derivatization, electronic circular dichroism (ECD) data. Putative biosynthetic pathways for these are proposed. Compounds 2, 3b, 6–8 showed...

Covalent ligands have attracted increasing attention due to their unique advantages, such as long residence time, high selectivity, and strong binding affinity. They also show promise for targets where previous efforts identify noncovalent small molecule inhibitors failed. However, our limited knowledge of covalent sites has hindered the discovery novel ligands. Therefore, developing in silico methods is highly desirable. Here, we propose DeepCoSI, first structure-based deep graph learning...

Abstract Accurate forecasting of traffic flow is crucial for intelligent control and guidance. It very challenging to forecast the due high non‐linearity, complexity dynamicity data. Most existing methods focus on designing complicated graph neural network architectures capture spatio‐temporal features data with help predefined graphs. However, exhibit a strong spatial dependency, which means that there are often complex correlations between nodes in road topology graph. Moreover, change...

Contemporary structure-based molecular generative methods have demonstrated their potential to model the geometric and energetic complementarity between ligands receptors, thereby facilitating design of molecules with favorable binding affinity target specificity. Despite introduction deep models for generation, atom-wise generation paradigm that partially contradicts chemical intuition limits validity synthetic accessibility generated molecules. Additionally, dependence learning on...

Species belonging to the genus Callicarpa are used traditionally in Chinese medicine for treatment of inflammation, rheumatism, and pain. Investigation leaves twigs bodinieri resulted isolation nine new abietane diterpenoids, bodinieric acids A–I (1–9), along with six known compounds (10–15). The structures 1–9 were elucidated on basis interpretation their HRESIMS NMR data by ECD calculations. To explore potential therapeutic target this plant immune-mediated disease, inhibitory activities...

Premnafulvol A (1), a unique diterpenoid featuring 6/5/7/3-fused tetracyclic carbon skeleton, with three biosynthetically related analogues, premnafulvols B–D (2–4), were isolated from the aerial parts of Premna fulva. Structures 1–4 established by combination extensive spectroscopic analyses, quantum chemical calculations, and X-ray crystallography. Plausible biosynthetic pathways proposed. Interestingly, 2 3 exhibited opposite effects on estrogen biosynthesis in human ovarian...

Fungal drug resistance is a major health threat, and reports of clinical worldwide are becoming increasingly common. In research program to discover new molecules help overcome this problem, 14 lanostane-type triterpenoids, gibbosicolids A–G (2–8) gibbosic acids I–O (9–15), were isolated from the fruiting bodies Ganoderma gibbosum, along with seven known triterpenoid derivatives. These compounds featured high levels oxidation, epimerization, γ-lactonization. Structures elucidated by...

A spiro ent-clerodane homodimer with a rare 6/6/6/6/6-fused pentacyclic scaffold, spiroarborin (1), together four new monomeric analogues (2-5), were isolated from Callicarpa arborea. Their structures elucidated by comprehensive spectroscopic data analysis, quantum-chemical calculations, and X-ray diffraction. plausible biosynthetic pathway of 1 was proposed, biomimetic synthesis its derivative accomplished. Compound showed potent inhibitory effect directly binding to the YEATS domain 11-19...

Investigation of the leaves and stems Premna szemaoensis resulted in isolation twelve new abietane diterpenoids, szemaoenoids A-L (1-12), together with four known diterpenoids (13-16). The structures involved two rearranged-abietane skeletons: 17(15 → 16)-abeo-abietane (7, 10-12, 14 15) 16),18(4 3)-diabeo-abietane (1-6, 13 16). compounds were established mainly by analyzing NMR HRESIMS data. absolute configurations 1, 3 10 confirmed single crystal X-ray diffraction analysis. In bioactivity...

Background and Objective . Colorectal cancer (CRC) is a common gastrointestinal tumour with high morbidity mortality. Endoscopic examination an effective method for early detection of digestive system tumours. However, due to various reasons, missed diagnoses misdiagnoses are occurrences. Our goal use deep learning methods establish colorectal lesion detection, positioning, classification models based on white light endoscopic images design computer-aided diagnosis (CAD) help physicians...

An active area of study under the dual carbon target, which is based on automatic identification systems (AIS), emission inventory pollutants from ships. Data compression required because there currently so much data that it has become difficult to transmit, process, and store it. A trajectory simplification method considering ship sailing state acceleration rate change developed in this paper assure validity compressed used analysis. By carefully examining integral relationship between...

Abstract Four new dolabellane-type diterpene alkaloids, glandulamines A – D (1 4), together with twelve known compounds (5 16), were isolated from the seeds of Nigella glandulifera using repeated column chromatography and semipreparative HPLC. The structures 1 16 elucidated based on NMR data analysis, HRMS experiments other spectroscopic interpretations. absolute configuration 5 was determined by single-crystal X-ray diffraction for first time. Compounds 10 12 showed human dihydroorotate...