18TH KREBS,HANS LECTURE - KNOWLEDGE-BASED PROTEIN MODELING AND DESIGN
18TH KREBS,HANS LECTURE - KNOWLEDGE-BASED PROTEIN MODELING AND DESIGN
复制标题
DOI：
10.1111/j.1432-1033.1988.tb13917.x
复制
发表时间：
1988-03-15
期刊：
影响因子：
--
通讯作者：
SUTCLIFFE, M
中科院分区：
文献类型：
--
作者：
BLUNDELL, T;CARNEY, D;SUTCLIFFE, M
描述了一种适用于药物、肽疫苗和新型蛋白质设计的蛋白质建模系统技术。我们的方法是基于知识的，取决于同源或类似蛋白质的结构，更一般地说，取决于蛋白质三维结构的关系数据库。该程序同时比对已知的三级结构，基于序列同源性从结构保守区域选择片段，将这些片段与“平均结构”或“框架”比对，建立在从同源蛋白质或更广泛的数据库中选择的环上，取代侧链，并且能量最小化所得模型。应用程序建模的同源结构，组织纤溶酶原激活剂的基础上，另一个丝氨酸蛋白酶，并模拟一个类似的蛋白质，HIV病毒蛋白酶的基础上，天冬氨酸蛋白酶，进行了说明。也解决了fab initiodesign的匡威问题：这涉及到选择氨基酸序列以给出特定的三级结构，在这种情况下是两个希腊钥匙基序的对称结构域。
A systematic technique for protein modelling that is applicable to the design of drugs, peptide vaccines and novel proteins is described. Our approach is knowledge‐based, depending on the structures of homologous or analogous proteins and more generally on a relational data base of protein three‐dimensional structures. The procedure simultaneously aligns the known tertiary structures, selects fragments from the structurally conserved regions on the basis of sequence homology, aligns these with the ‘average structure’ or ‘framework’, builds on the loops selected from homologous proteins or a wider database, substitutes sidechains and energy minimises the resultant model. Applications to modelling an homologous structure, tissue plasminogen activator on the basis of another serine proteinase, and to modelling an analogous protein, HIV viral proteinase on the basis of aspartic proteinases, are described. The converse problem ofab initiodesign is also addressed: this involves the selection of an amino acid sequence to give a particular tertiary structure, in this case a symmetrical domain of two Greek‐key motifs.