A virtual library of constrained cyclic tetrapeptides that mimics all four side-chain orientations for over half the reverse turns in the protein data bank
A virtual library of constrained cyclic tetrapeptides that mimics all four side-chain orientations for over half the reverse turns in the protein data bank
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DOI：
10.1007/s10822-008-9241-4
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发表时间：
2009-02-01
影响因子：
3.5
通讯作者：
Marshall, Garland R.
中科院分区：
文献类型：
--
作者：
Arbor, Sage;Marshall, Garland R.
反向转角通常是蛋白质/蛋白质相互作用的识别位点，因此，在开发潜在的治疗剂中，是用于确定识别基序的有价值的潜在靶标。产生了环状四肽（CTP）的虚拟组合文库，并且低能结构中的键与典型的反转C α-C β键重叠（Tran等人，J Comput Aided Mol Des 19（8）：551-566，2005）以确定CTP作为反向转角肽模拟物的效用。蛋白质数据库（PDB）中的所有反转，晶体结构分辨率为千分之一货币符号3.0 A...被分类为相同的已知典型的反转C α-C β键簇（Tran等人，J Comput Aided Mol Des 19（8）：551-566，2005）。编制了CTP反转模拟物，模拟了PDB反转中四个C α-C β键中的三个以及所有四个C α-C β键的相对方向。PDB中表示的54%的反向转角具有八个或更多个CTP结构，其模拟反向转角中所有四个C α-C β键的取向。
Reverse turns are often recognition sites for protein/protein interactions and, therefore, valuable potential targets for determining recognition motifs in development of potential therapeutics. A virtual combinatorial library of cyclic tetrapeptides (CTPs) was generated and the bonds in the low-energy structures were overlapped with canonical reverse-turn C alpha-C beta bonds (Tran et al., J Comput Aided Mol Des 19(8):551-566, 2005) to determine the utility of CTPs as reverse-turn peptidomimetics. All reverse turns in the Protein Data Bank (PDB) with a crystal structures resolution a parts per thousand currency sign3.0 A... were classified into the same known canonical reverse-turn C alpha-C beta bond clusters (Tran et al., J Comput Aided Mol Des 19(8):551-566, 2005). CTP reverse-turn mimics were compiled that mimicked both the relative orientations of three of the four as well as all four C alpha-C beta bonds in the reverse turns of the PDB. 54% of reverse turns represented in the PDB had eight or more CTPs structures that mimicked the orientation of all four of the C alpha-C beta bonds in the reverse turn.