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Protein kinase 2 (CK2) is a potential target, and the coumarins were identified as the attractive CK2 inhibitors. In this study, two models (CoMFA and CoMSIA) were established, and their reliabilities were supported by statistical parameters. From the CoMFA and CoMSIA models, the hydrophobic and hydrogen bonds play very important roles in the interactions between inhibitors and CK2, which were confirmed sufficiently by molecular docking. Furthermore, the binding mode of the inhibitors at the active sites of CK2 was also investigated by docking study. The hydroxyl at the position R(5) is more important for coumarins inhibitors because it forms hydrogen bonds not only with Lys68 as hydrogen acceptor but also with H(2) O as hydrogen donor. In addition, hydroxyl can make electrostatic interactions with electropositive Lys68 residue. The large group at the R(6) position is not conducive to inhibitor dock into the groove of the binding site of CK2. When there is nitro group, the electrostatic interaction between ligand and receptor is enhanced significantly, and the nitro oxygen can form hydrogen bonds with the backbone NH of Lys68 and Asp175 simultaneously. The results obtained from molecular modeling techniques not only provide the models to predict the activity of inhibitors but also lead to a better understanding of the interactions between inhibitors and CK2, which will be very helpful for drug design.

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BackgroundThyroid-associated ophthalmopathy (TAO) is one of the most common orbital diseases that seriously threatens visual function and significantly affects patients’ appearances, rendering them unable to work. This study established an intelligent diagnostic system for TAO based on facial images.MethodsPatient images and data were obtained from medical records of patients with TAO who visited Shanghai Changzheng Hospital from 2013 to 2018. Eyelid retraction, ocular dyskinesia, conjunctival congestion, and other signs were noted on the images. Patients were classified according to the types, stages, and grades of TAO based on the diagnostic criteria. The diagnostic system consisted of multiple task-specific models.ResultsThe intelligent diagnostic system accurately diagnosed TAO in three stages. The built-in models pre-processed the facial images and diagnosed multiple TAO signs, with average areas under the receiver operating characteristic curves exceeding 0.85 (F1 score >0.80).ConclusionThe intelligent diagnostic system introduced in this study accurately identified several common signs of TAO.

Heat shock protein 90 (Hsp90) takes part in the developments of several cancers. Novobiocin, a typically C-terminal inhibitor for Hsp90, will probably used as an important anticancer drug in the future. In this work, we explored the valuable information and designed new novobiocin derivatives based on a three-dimensional quantitative structure-activity relationship (3D QSAR). The comparative molecular field analysis and comparative molecular similarity indices analysis models with high predictive capability were established, and their reliabilities are supported by the statistical parameters. Based on the several important influence factors obtained from these models, six new novobiocin derivatives with higher inhibitory activities were designed and confirmed by the molecular simulation with our models, which provide the potential anticancer drug leads for further research.

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