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Kaixian Chen

Bio: Kaixian Chen is an academic researcher from Chinese Academy of Sciences. The author has contributed to research in topics: Virtual screening & Docking (molecular). The author has an hindex of 47, co-authored 380 publications receiving 9209 citations. Previous affiliations of Kaixian Chen include Shanghai University & East China University of Science and Technology.


Papers
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Journal Article
TL;DR: The proposed interaction mechanism is helpful for further mutant experiments and designing novel potent kappa-opioid agonists.
Abstract: AIM: To study the interaction between kappa-opioid receptor and its nonpeptide agonists. METHODS: The ""conservation patterns"" for G-protein coupled receptors (GPCR) were used to determine 7 transmembrane (TM) regions. Taking the crystallographic coordinates of bacteriorhodopsin (BR) as the template, the 3D structural model was constructed for 7 TM of kappa-opioid subtype with molecular mechanics (MM) method. Five highly active nonpeptide kappa-opioid agonists were docked into the 7 helices of kappa-opioid receptor to study the ligand-receptor interaction. RESULTS: Four important interactions between U-50488-like agonists and kappa-opioid receptors were drawn according to our modeling study: (1) the protonated pyrrolidine nitrogen of the ligands formed a hydrogen-bond with the carboxyl of Asp138; (2) the carbonyl oxygen of ligands forms a hydrogen bond to the hydroxyl of Ser187; (3) the aryl groups connected to acylamide of the agonists inserted into a hydrophobic cavity enclosed by residues Val239, Val236, Phe235, Val232, Leu186, and Trp183; (4) the pyrrolidine of the ligands in the complexes was surrounded by Ile290, Asp138, Ile194, Ile135, and Cys131. CONCLUSION: The proposed interaction mechanism is helpful for further mutant experiments and designing novel potent kappa-opioid agonists.

4 citations

Journal ArticleDOI
TL;DR: K i values of some typical ligands of PParγ were successfully determined by use of the equations derived, among which the K i value of PPARγ-LY171883 was reported for the first time.
Abstract: Upon the study of small-molecules binding to proteins, the traditional methods for calculating dissociation constants (K d and K i ) have shortcomings in dealing with the single binding site models. In this paper, two equations have been derived to solve this problem. These two equations are independent of the total concentration or initial degree of saturation of receptor and the activity of the competitive molecule. Through nonlinear fitting against these two equations, K d value of a probe can be obtained by binding assay, and K i value of a ligand can be obtained by competitive assay. Moreover, only the total concentrations of receptor([R]t), ligand([L]t) and probe([P]t) are required for the data fitting. In this work, K i values of some typical ligands of PPARγ were successfully determined by use of our equations, among which the K i value of PPARγ-LY171883 was reported for the first time.

4 citations

Journal Article
TL;DR: The correlations derived from CoMFA analysis with the four alignments proved all to have good predictive values and indicated that the side chain of -C6-O2-O1-C10-O3-C7-O4-C12-O5- and atom C16 are important groups of artemisinin analogs for antimalarial activity.
Abstract: Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (3D-QSAR) paradigm, was used to study the correlations between the physicochemical properties and the in vitro activities of a series of ether and ester analogs of artemisinin. Four alignment models were used in the CoMFA investigation. The correlations derived from CoMFA analysis with the four alignments proved all to have good predictive values. The steric field predictive model of alignment B is accordant with the experimental results of Avery M A, et al: J Med Chem 1993; 36: 4264-75. The electrostatic field predictive results of alignments A, B, and C are consistent with our previous result of quantum chemical calculation. The highest rcross2 of alignment D, indicated that the side chain of -C6-O2-O1-C10-O3-C7-O4-C12-O5- and atom C16 are important groups of artemisinin analogs for antimalarial activity.

4 citations

Journal ArticleDOI
TL;DR: The discovery of triazoloquinoxaline 1a is described as a novel STING agonist possessing the potential to be further developed for antiviral and antitumor treatment via Structure-based Virtual Screening.

4 citations

Journal ArticleDOI
Yu Feng1, Dongxiang Liu1, Xu Shen1, Kaixian Chen1, Hualiang Jiang1 
TL;DR: The results indicated that Bcl-x(L) dimer trapped by cross-linking in lipids is distinct from the domain swapped dimer, suggesting that B Cl-x (L) transits through a structural change from the water-soluble state to the membrane-bound state and there are multiple possibilities for structural reorganization of B cl-x-L) protein.

4 citations


Cited by
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Christopher M. Bishop1
01 Jan 2006
TL;DR: Probability distributions of linear models for regression and classification are given in this article, along with a discussion of combining models and combining models in the context of machine learning and classification.
Abstract: Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

10,141 citations

01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

4,833 citations

Journal ArticleDOI
TL;DR: This review covers the literature published in 2014 for marine natural products, with 1116 citations referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms.

4,649 citations

Journal ArticleDOI
11 Jun 2020-Nature
TL;DR: A programme of structure-assisted drug design and high-throughput screening identifies six compounds that inhibit the main protease of SARS-CoV-2, demonstrating the ability of this strategy to isolate drug leads with clinical potential.
Abstract: A new coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the aetiological agent responsible for the 2019–2020 viral pneumonia outbreak of coronavirus disease 2019 (COVID-19)1–4. Currently, there are no targeted therapeutic agents for the treatment of this disease, and effective treatment options remain very limited. Here we describe the results of a programme that aimed to rapidly discover lead compounds for clinical use, by combining structure-assisted drug design, virtual drug screening and high-throughput screening. This programme focused on identifying drug leads that target main protease (Mpro) of SARS-CoV-2: Mpro is a key enzyme of coronaviruses and has a pivotal role in mediating viral replication and transcription, making it an attractive drug target for SARS-CoV-25,6. We identified a mechanism-based inhibitor (N3) by computer-aided drug design, and then determined the crystal structure of Mpro of SARS-CoV-2 in complex with this compound. Through a combination of structure-based virtual and high-throughput screening, we assayed more than 10,000 compounds—including approved drugs, drug candidates in clinical trials and other pharmacologically active compounds—as inhibitors of Mpro. Six of these compounds inhibited Mpro, showing half-maximal inhibitory concentration values that ranged from 0.67 to 21.4 μM. One of these compounds (ebselen) also exhibited promising antiviral activity in cell-based assays. Our results demonstrate the efficacy of our screening strategy, which can lead to the rapid discovery of drug leads with clinical potential in response to new infectious diseases for which no specific drugs or vaccines are available. A programme of structure-assisted drug design and high-throughput screening identifies six compounds that inhibit the main protease of SARS-CoV-2, demonstrating the ability of this strategy to isolate drug leads with clinical potential.

2,845 citations

Journal ArticleDOI
TL;DR: A number of substructural features which can help to identify compounds that appear as frequent hitters (promiscuous compounds) in many biochemical high throughput screens are described.
Abstract: This report describes a number of substructural features which can help to identify compounds that appear as frequent hitters (promiscuous compounds) in many biochemical high throughput screens. The compounds identified by such substructural features are not recognized by filters commonly used to identify reactive compounds. Even though these substructural features were identified using only one assay detection technology, such compounds have been reported to be active from many different assays. In fact, these compounds are increasingly prevalent in the literature as potential starting points for further exploration, whereas they may not be.

2,791 citations