Abstract: The low-voltage activated T-type calcium channels regulate cellular excitability and oscillatory behavior of resting membrane potential which trigger many physiological events and have been implicated with many diseases. Here, we determine structures of the human T-type CaV3.3 channel, in the absence and presence of antihypertensive drug mibefradil, antispasmodic drug otilonium bromide and antipsychotic drug pimozide. CaV3.3 contains a long bended S6 helix from domain III, with a positive charged region protruding into the cytosol, which is critical for T-type CaV channel activation at low voltage. The drug-bound structures clearly illustrate how these structurally different compounds bind to the same central cavity inside the CaV3.3 channel, but are mediated by significantly distinct interactions between drugs and their surrounding residues. Pho...

  Abstract： We report for the first time the use of experimental electron density (ED) in the Protein Data Bank for modeling of noncovalent interactions (NCIs) for protein–ligand complexes. Our methodology is based on reduced electron density gradient (RDG) theory describing intermolecular NCIs by ED and its first derivative. We established a database named Experimental NCI Database (ExptNCI; http://ncidatabase.stonewise.cn/#/nci) containing ED saddle points, indicating ∼200,000 NCIs from over 12,000 protein–ligand complexes. We also demonstrated the usage of the database in the case of depicting amide−π interactions in protein–ligand binding systems. In summary, the database provides details on experimentally observed NCIs for protein–ligand complexes and can support future studies including studies o...

  Abstract： The increasing literature leads to formidable pressure for medical researchers. Most existing recommender approaches mainly depend on text-based information. How to extract and utilize the heterogeneous information, especially the graphic ones, to improve the recommender is worthy of further exploring. To this end, we establish a document-to-document recommender system for medical literature (D2D-MR). Specifically, we proposed HB-GED, the Half-branch GED algorithm, and the bipartite-graph-based algorithm for solving the molecule similarity and the paper similarity, respectively. Experimental results on real-world datasets demonstrate the effectiveness of the proposed recommender system. The Full Article Link: Doc-to-Doc Recommender for Medical Literature with Similarity of Molecule Graphs | IEEE Conference Publication | IEEE...

Abstract: Molecular scaffolds are widely used in drug design. Many methods and tools have been developed to utilize the information in scaffolds. Scaffold diversification is frequently used by medicinal chemists in tasks such as lead compound optimization, but tools for scaffold diversification are still lacking. Here, we propose AIScaffold , a web-based tool for scaffold diversification using the deep generative model. This tool can perform large-scale (up to 500,000 molecules) diversification in several minutes and recommend the top 500 (top 0.1%) molecules. Features such as site-specific diversification are also supported. This tool can facilitate the scaffold diversification process for medicinal chemists, thereby accelerating drug design. The Full Article Link: Journal of Chemical Information and Modeling | Vol 61, No 1 (acs.org)