蛋白质别构调控分子设计
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- 英文论文题名：Protein Allosteric Ligand Design
- 论文作者：来鲁华
- 英文论文作者：Luhua Lai ; BNLMS ; State Key for Structural Chemistry of Unstable and Stable Species ; College of Chemistry and Molecular Engineering ; Peking University
- 年：2016
- 作者机构：北京大学化学与分子工程学院,北京分子动态与稳态国家重点实验室,分子科学国家实验室;
- 论文关键词：蛋白质 ; 别构调控 ; 别构位点预测 ; 别构分子设计
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：O629.73
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：137k
- 原文格式：D
- 会议级别：全国
摘要
蛋白质的别构调控是指可以通过远距离处的扰动来调控蛋白质的活性,这种扰动可以通过配体结合、共价修饰、甚至是对于蛋白质作用网络中其它蛋白质的影响来实现。针对别构效应的药物设计近年来受到了广泛关注,其主要优点为别构调控配体不与内源的配体或底物直接竞争且会有更好的选择性。目前已知的绝大多数别构调控分子都是实验筛选发现的,如何有针对性地进行蛋白质功能的别构调控仍然面临很大困难。我们发展了在蛋白质结构中发现潜在别构调控位点的计算方法,并在多个蛋白质体系的激活剂或抑制剂研究中得到成功应用。在15-脂氧酶等体系中发现了作用于同一别构位点的激活剂与抑制剂,为深入探讨该蛋白质的活性调控机理提供了分子探针。
Protein allosteric regulation refers to perturbation at a distance that makes remarkable influence on function,which can be produced through ligand binding,posttranslational modification,or changes in other proteins in the biological network.Allosteric drugs have attracted much attention,as they do not compete with endogenous ligands and with high specificity than orthosteric drugs.Most of the known allosteric ligands came from large scale experimental screenings.Rational design of allosteric ligands remains challenging.We have studied protein allosteric mechanism and developed strategies for allosteric site identification and allosteric ligand design.In several protein systems,we were able to identify molecules that can either activate or inhibit protein activity.These allosteric ligands serve as molecule probes for protein function regulation studies.
Protein allosteric regulation refers to perturbation at a distance that makes remarkable influence on function,which can be produced through ligand binding,posttranslational modification,or changes in other proteins in the biological network.Allosteric drugs have attracted much attention,as they do not compete with endogenous ligands and with high specificity than orthosteric drugs.Most of the known allosteric ligands came from large scale experimental screenings.Rational design of allosteric ligands remains challenging.We have studied protein allosteric mechanism and developed strategies for allosteric site identification and allosteric ligand design.In several protein systems,we were able to identify molecules that can either activate or inhibit protein activity.These allosteric ligands serve as molecule probes for protein function regulation studies.
引文
[1]Meng,H..;Liu,Y.;Lai,L.Acc.Chem.Res.2015,48:2242.
[2]Ma X.;Qi,Y.;Lai,L.Proteins 2015,83:1375.
[3]Meng H.;McClendon C.L.;Dai Z.;Li K.;Zhang X.;He S.;Shang E.;Liu Y.;Lai L.J.Med.Chem.2016,in press.DOI:10.1021/acs.jmedchem.5b01011.
[4]Qi,Y.;Wang,Q.;Tang,B.;Lai,L.J.Chem.Theory Comput.2012,8:2962
[2]Ma X.;Qi,Y.;Lai,L.Proteins 2015,83:1375.
[3]Meng H.;McClendon C.L.;Dai Z.;Li K.;Zhang X.;He S.;Shang E.;Liu Y.;Lai L.J.Med.Chem.2016,in press.DOI:10.1021/acs.jmedchem.5b01011.
[4]Qi,Y.;Wang,Q.;Tang,B.;Lai,L.J.Chem.Theory Comput.2012,8:2962