期刊：
STAR Protocols,2021年2(1):100312 ISSN：2666-1667
通讯作者：
Gefei Hao
作者机构：
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China;International Joint Research Center for Intelligent Biosensor Technology and Health, Central China Normal University, Wuhan 430079, China;State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Research and Development Center for Fine Chemicals, Guizhou University, Guiyang 550025, China;Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China;[Guangfu Yang] Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China<&wdkj&>International Joint Research Center for Intelligent Biosensor Technology and Health, Central China Normal University, Wuhan 430079, China<&wdkj&>Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China
通讯机构：
[Gefei Hao] K;Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, China<&wdkj&>International Joint Research Center for Intelligent Biosensor Technology and Health, Central China Normal University, Wuhan 430079, China<&wdkj&>State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Research and Development Center for Fine Chemicals, Guizhou University, Guiyang 550025, China
摘要：
Hit-to-lead (H2L) optimization is crucial for drug design, which has become an increasing concern in medicinal chemistry. A virtual screening strategy of auto in silico ligand directing evolution (AILDE) has been developed to yield promising lead compounds rapidly and efficiently. The protocol includes instructions for fragment compound library construction, conformational sampling by molecular dynamics simulation, ligand modification by fragment growing, as well as the binding free energy prediction.
For complete details on the use and execution of this protocol, please refer to Wu et al. (2020).
期刊：
BRIEFINGS IN BIOINFORMATICS,2021年22(1):605-605 ISSN：1467-5463
通讯作者：
Hao, G.-F.;Yang, G.-F.
作者机构：
[Yang, Guang-Fu; Yang, Jing-Fang; Wang, Fan; Hao, Ge-Fei] Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P.R.China;International Joint Research Center for Intelligent Biosensor Technology and Health, Central China Normal University，Wuhan, 430079, China;[Hao, Ge-Fei] State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Research and Development Center for Fine Chemicals, Guizhou University, Guiyang 550025, P. R. China;[Yang, Guang-Fu] Collaborative Innovation Center of Chemical Science and Engineering, Tianjing 300072, P.R.China;[Chen, Yu-Zong] Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543
通讯机构：
[Hao, G.-F.; Yang, G.-F.] K;[Hao, G.-F.; Yang, G.-F.] I;[Hao, G.-F.] S;[Yang, G.-F.] C;Key Laboratory of Pesticide & Chemical Biology , Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P.R. China<&wdkj&>International Joint Research Center for Intelligent Biosensor Technology and Health , Central China Normal University，Wuhan, 430079, China<&wdkj&>Collaborative Innovation Center of Chemical Science and Engineering , Tianjing 300072, P.R. China<&wdkj&>Key Laboratory of Pesticide & Chemical Biology , Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P.R. China<&wdkj&>International Joint Research Center for Intelligent Biosensor Technology and Health , Central China Normal University，Wuhan, 430079, China<&wdkj&>State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering , Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Research and Development Center for Fine Chemicals, Guizhou University, Guiyang 550025, P. R. China
摘要：
Aims and ScopeBulletin of Experimental Biology and Medicine a translation of Byulleitin Eksperimental noi Biologii iMeditsiny, publishes the latest experimental research on key issuesin modern biology and medicine.The Russian Volume Year is published in English from April.Coverage in the Journals&commat;Ovid database begins with the September 2000 issue.
作者机构：
[Guang-Fu Yang; Jing-Fang Yang; Ge-Fei Hao] Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan Hubei;430079, China;Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Research and Development Center for Fine Chemicals, Guizhou University, Guiyang Guizhou;550025, China;International Joint Research Center for Intelligent Biosensor Technology and Health, Central China Normal University, Wuhan Hubei
通讯机构：
[Ge-Fei Hao; Guang-Fu Yang] K;Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079, People’s Republic of China<&wdkj&>International Joint Research Center for Intelligent Biosensor Technology and Health, Central China Normal University, Wuhan, Hubei 430079, People’s Republic of China<&wdkj&>Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, People’s Republic of China<&wdkj&>Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079, People’s Republic of China<&wdkj&>State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Research and Development Center for Fine Chemicals, Guizhou University, Guiyang, Guizhou 550025, People’s Republic of China
期刊：
Drug Discovery Today,2020年25(1):248-258 ISSN：1359-6446
通讯作者：
Jia, Chen-Yang
作者机构：
[Yang, Guang-Fu; Li, Jing-Yi; Jia, Chen-Yang; Hao, Ge-Fei] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu; Hao, Ge-Fei] Cent China Normal Univ, Int Joint Res Ctr Intelligent Biosensor Technol &, Wuhan 430079, Peoples R China.;[Hao, Ge-Fei] Guizhou Univ, State Key Lab Breeding Base Green Pesticide & Agr, Key Lab Green Pesticide & Agr Bioengn, Minist Educ,Res & Dev Ctr Fine Chem, Guiyang 550025, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300072, Peoples R China.
通讯机构：
[Jia, Chen-Yang] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
摘要：
Undesirable pharmacokinetic (PK) properties or unacceptable toxicity are the main causes of the failure of drug candidates at the clinical trial stage. Since the concept of drug-likeness was first proposed, it has become an important consideration in the selection of compounds with desirable bioavailability during the early phases of drug discovery. Over the past decade, online resources have effectively facilitated drug-likeness studies in an economical and time-efficient manner. Here, we provide a comprehensive summary and comparison of current accessible online resources, in terms of their key features, application fields, and performance for in silico drug-likeness studies. We hope that the assembled toolbox will provide useful guidance to facilitate future in silico drug-likeness research.
作者机构：
[Yang, Guang-Fu; Yang, Jing-Fang; Hao, Ge-Fei; Yang, GF] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu; Yang, Jing-Fang; Hao, Ge-Fei; Yang, GF] Cent China Normal Univ, Int Joint Res Ctr Intelligent Biosensor Technol &, Wuhan 430079, Peoples R China.;[Chen, Mo-Xian; Zhang, Jian-Hua] Chinese Univ Hong Kong, Shenzhen Res Inst, Shenzhen 300072, Peoples R China.;[Zhang, Jian-Hua] Hong Kong Baptist Univ, Dept Biol, Kowloon Tong, Hong Kong 300072, Peoples R China.;[Zhang, Jian-Hua] Chinese Univ Hong Kong, State Key Lab Agrobiotechnol, Shatin, Hong Kong 300072, Peoples R China.
通讯机构：
[Yang, Guang-Fu; Hao, GF; Yang, GF] C;[Hao, Ge-Fei] G;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.;Cent China Normal Univ, Int Joint Res Ctr Intelligent Biosensor Technol &, Wuhan 430079, Peoples R China.;Guizhou Univ, Res & Dev Ctr Fine Chem, State Key Lab Breeding Base Green Pesticide & Agr, Minist Educ,Key Lab Green Pesticide & Agr Bioengn, Guiyang 550025, Peoples R China.
关键词：
Abscisic acid;evolution;functional divergence;phylogenetic;positive selection;PYR1 (Pyrabactin Resistance 1)/PYRL (PYR-Like)/RCAR (Regulatory Component of ABA Receptor)
摘要：
The plant hormone abscisic acid (ABA) plays a crucial role during the plant life cycle as well as in adaptive responses to environmental stresses. The core regulatory components of ABA signaling in plants are the pyrabactin resistance1/PYR1-like/regulatory ABA receptors (PYLs for simplicity) comprise the largest plant hormone receptor family known. They act as negative regulators of members of the protein phosphatases type 2C family (PP2Cs). Due to the biological importance of PYLs, many researchers have focused on their genetic redundancy and consequent functional divergence. However, little is understood of their evolution and its impact on the generation of regulatory diversity. In this study, we identi fi ed positive selection and function divergency in PYLs through phylogenetic reconstruction, gene structure and expression pattern analysis, positive selection analysis, functional divergence analysis, and structure comparison. We found correlation of desensitization of PYLs with specific modifications in the molecular recognition domain with functional diversification. Hence, an interesting antagonistic coevolution mechanism is proposed, which results in the functional diversification of ABA receptor family proteins. We believe a compensatory evolutionary pathway may have occurred.
摘要：
Succinate dehydrogenase (SDH) also known as complex II or succinate:quinone oxidoreductase is an enzyme involved in both oxidative phosphorylation and tricarboxylic acid cycle; the processes that generate energy. SDH is a multi-subunit enzyme which requires a series of proteins for its proper assembly at several steps. This enzyme has medical significance as there is a broad range of human diseases from cancers to neurodegeneration related to SDH malfunction. Some of these disorders have recently been linked to defective assembly factors, reinvigorating further research in this area. Apart from that this enzyme has agricultural importance as many fungicides have been/will be designed targeting specifically this enzyme in plant fungal pathogens. In addition, we speculate it might be possible to design novel fungicides specifically targeting fungal assembly factors. Considering the medical and agricultural implications of SDH, the aim of this review is an overview of the SDH assembly factors and critical analysis of controversial issues around them.
通讯机构：
[Yang, WC; Yang, GF; Yang, Guang-Fu] C;Cent China Normal Univ, Minist Educ, Coll Chem, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 30071, Peoples R China.
摘要：
We report herein the structure-based design and application of a fluorogenic molecular probe (BChE-FP) specific to butyrylcholinesterase (BChE). This probe was rationally designed by mimicking the native substrate and optimized stepwise by manipulating the steric feature and the reactivity of the designed probe targeting the structural difference of the active pockets of BChE and AChE. The refined probe, BChE-FP, exhibits high specificity toward BChE compared to AChE, producing about 275-fold greater fluorescence enhancement upon the catalysis by BChE. Thus, BChE-FP is a specific BChE probe identified by the structure-based design and it can discriminate BChE from AChE. Furthermore, it has been successfully applied for imaging the endogenous BChE in living cells, as well as BChE inhibitor screening and characterization under physiological conditions.
摘要：
Functionalized 6-arylsalicylate substructures occur in a variety of pharmacologically relevant natural products and bioactive compounds. Especially 6-arylsubstituted salicylates, as a key pharmacophore of anti-resistant acetohydroxyacid synthase (AHAS) inhibitors have played a lead role in combatting the weed-resistance issues. Previously, we have explored two new methods to synthesize position-6 aryl substituted salicylic acid fragment. However, these two methods failed to introduce various substituents into salicylic acid. Here an efficient method for the synthesis of 6-substituted salicylates is described via a microwave-promoted Suzuki cross-coupling. Due to the obvious advantages of this method, such as a wide range of substrates, smooth and rapid reaction and moderate to excellent yields, this protocol could be utilized to synthesize more anti-resistant AHAS inhibitors.
