作者机构：
[Wan, Jian; Rao, Li; Wei, Lin; Hu, Saiya; Ren, Yanliang; Wan, J; Song, Rongrong; Huang, Yunyuan; Lei, Mengting; Wen, Wuqiang] Cent China Normal Univ, Int Cooperat Base Pesticide & Green Synth Hubei, Key Lab Pesticide & Chem Biol CCNU, Minist Educ,Dept Chem, Wuhan 430079, Peoples R China.;[Liu, Kai] Guangxi Univ Chinese Med, Inst Marine Drugs, Nanning 530200, Peoples R China.
通讯机构：
[Ren, YL; Wan, J] C;Cent China Normal Univ, Int Cooperat Base Pesticide & Green Synth Hubei, Key Lab Pesticide & Chem Biol CCNU, Minist Educ,Dept Chem, Wuhan 430079, Peoples R China.
摘要：
De novo drug design actively seeks to use sets of chemical rules for the fast and efficient identification of structurally new chemotypes with the desired set of biological properties. Fragment-based de novo design tools have been successfully applied in the discovery of noncovalent inhibitors. Nevertheless, these tools are rarely applied in the field of covalent inhibitor design. Herein, we present a new protocol, called Cov_FB3D, which involves the in silico assembly of potential novel covalent inhibitors by identifying the active fragments in the covalently binding site of the target protein. In this protocol, we propose a BA-SAMP strategy, which combines the noncovalent moiety score with the X-Score as the molecular mechanism (MM) level, and the covalent candidate score with the PM7 as the QM level. The synthetic accessibility of each suggested compound could be further evaluated with machine-learning-based synthetic complexity evaluation (SCScore). An in-depth test of this protocol against the crystal structures of 15 covalent complexes consisting of BTK inhibitors, KRAS inhibitors, EGFR inhibitors, EphB1 inhibitors, MAGL inhibitors, and MAPK inhibitors revealed that most of these inhibitors could be de novo reproduced from the fragments by Cov_FB3D. The binding modes of most generated reference poses could accurately reproduce the known binding mode of most of the reference covalent adduct in the binding site (RMSD <= 2 angstrom). In particular, most of these inhibitors were ranked in the top 2%, using the BA-SAMP strategy. Notably, the novel human ALDOA inhibitor (T1) with potent inhibitory activity (0.34 +/- 0.03 mu M) and greater synthetic accessibility was successfully de novo designed by this protocol. The positive results confirm the abilities of Cov_FB3D protocol.
作者机构：
[Jian Wan; Yanliang Ren] Key Laboratory of Pesticide & Chemical Biology(CCNU),Ministry of Education,Department of Chemistry,Central China Normal University
会议名称：
中国化学会第九届全国有机化学学术会议
会议时间：
2015-07-28
会议地点：
中国吉林长春
摘要：
<正>ClassⅡfructose bis-phosphate aldolases(FBA-Ⅱ)are potential and particularly attractive new targets for the discovery of drugs to combat invasive bacterial and fungal infection,because of their occu
作者机构：
[Jian Wan; Yanliang Ren] Key Laboratory of Pesticide & Chemical Biology (CCNU),Ministry of Education,College of Chemistry,Central China Normal University
摘要：
Cyanobacteria harmful algal blooms (HABs) pose an increasingly serious water pollution problem all over the world.Class Ⅱ Fructose-l,6-bisphoshate aldolase (Cy-FBA-Ⅱ) and cyanobacteria Fructose-l,6-Bisphosphatase (Cy-FBPase) are two neighbouring key regulatory enzymes in Calvin cycle of cyanobacteria photosynthesis system.Each of them might be taken as the potential target for designing novel inhibitors to chemically control harmful algal blooms (HABs).In the present paper, a series of novel inhibitors were designed, synthesized and optimized based upon the structural and interactional information of both Cy-FBA-Ⅱ and Cy-FBPase, and their inhibitory activities were examined in vitro and in vivo.The experimental results showed that compounds L20a-L20d exhibited high Cy-FBA-Ⅱ inhibitory activity (IC50 =2.3-5.7 μM) and moderate Cy-FBPase inhibitory activity (IC50 =92.0-140.1 μM), however, compounds L20e-L20h could potentially inhibit both of Cy-FBA-Ⅱ and Cy-FBPase with IC50 values less than 30 μM, which demonstrate more or less dual-target inhibitor's feature.Moreover, most of them exhibited high algicide activity (EC50 =0.8-15.3 ppm) against cyanobacteria Synechocystis sp.PCC 6803.
摘要：
In the first part,the energy transfer pathways in trimeric and hexameric aggregation state of cyanobacteria C-phycocyanin(C-PC)were investigated in the framework of F?rster model.Only when the protona
摘要：
<正>In the present study, the electronic energy transfer rates in C-phycocyanin (C-PC) trimer and hexamer were investigated by jointly using F rster theory and time-dependent density functional theory.
作者机构：
[Jian Wan] Key Laboratory of Pesticide & Chemical Biology(CCNU),Ministry of Education,Department of Chemistry,Central China Normal University,Wuhan,430079,P.R.China
作者机构：
[Jian Wan; Yanliang Ren; Ke Wei; Yongjian Li] Key Laboratory of Pesticide & Chemical Biology(CCNU), Ministry of Education;Department of Chemistry, Central China Normal University, Wuhan 430079, China;[Xin Xu] State Key Laboratory for Physical Chemistry of Solid Surfaces;College for Chemistry and Chemical Engineering, Center for Theoretical Chemistry, Xiamen University, Xiamen 361005, China;[Jian Wan; Yanliang Ren; Ke Wei; Yongjian Li] Department of Chemistry, Central China Normal University, Wuhan 430079, China
作者机构：
[万坚] Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education;[万坚] College of Chemistry, Central China Normal University
会议名称：
中国上海第七届国际新药发明科技年会
会议时间：
2009-10-22
会议地点：
上海
会议主办单位：
中国医药生物技术协会
会议论文集名称：
中国上海第七届国际新药发明科技年会论文集
摘要：
A detailed description of the molecular mechanism for the interactions between enzyme and its ligands (catalytic substrate or inhibitors) is of central importance for structure-based inhibitor design and virtual screening.In the absence of the crystallographic structure of the target enzyme,a combine of molecular modeling and bio-techniques (clone,expression,purification,site-directed mutation) becomes an alternatively useful tool in obtaining the information of the interactions.Jointly with the experimental bio-affinity data at enzyme level in vitro,a developed molecular docking-based three-dimensional qualitative structure-activity relationship (3D-QSAR) modeling scheme is put forward not only for getting the information of binding interaction of the active site,but also for employing it as a complementary scoring function in virtual screening.This strategy is expected to practically improve the quality of virtual screening.
作者机构：
[Jian Wan; Lingling Feng; Jingmei Jiao; Weiwei Wang; Li Zhou; Guangyuan Liang; Kai Liu; Ding Li] Key Laboratory of Pesticide & Chemical Biology(CCNU), Ministry of Education;College of Chemistry, Central China Normal University, Wuhan 430079, P R China;[Jian Wan; Lingling Feng; Jingmei Jiao; Weiwei Wang; Li Zhou; Guangyuan Liang; Kai Liu; Ding Li] College of Chemistry, Central China Normal University, Wuhan 430079, P R China
作者机构：
[Jian Wan; Lingling Feng; Qingye Zhang; Ding Li; Pei Wei; Jie Zhang; Yangliang Ren; Zhigang Chen; Deli Liu; Ziniu Yu] Key Laboratory of Pesticide & Chemical Biology(CCNU),Ministry of Education,College of Chemistry,Central China Normal University,Wuhan 430079,P R China
作者机构：
[万坚] Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education;[万坚] College of Chemistry, Central China Normal University
会议名称：
中国化学会第27届学术年会
会议时间：
2010-06-20
会议地点：
中国福建厦门
会议论文集名称：
中国化学会第27届学术年会第15分会场摘要集
摘要：
<正>Cytochrome P450 sterol 14α-demethylases （CYP51s） are essential enzymes in sterol biosynthesis and well known as the target of antifungal drugs. All fungal CYP51s are
摘要：
p-tert-Butylcalix[7]arene reacting with phosphorus pentachloride and then with water afforded two stereoisomers p-tert-butylcalix[7]arene diphosphates 2a and 2b, representing the first phosphorus multiple bridged calix[7]arene. The more accurate structure of 2a was investigated with the aid of Gaussian03 calculations.
