摘要
采用多重拷贝同时搜寻(MCSS)等方法对Bcl-2蛋白抑制剂结合腔进行分析.结果显示,结合腔可分成P1,L1,P2,P3和P4等5个区域,其底部呈疏水性,而P3部位不适合芳香性大基团的结合.结合腔侧面和边缘处分布有可与配体形成除疏水以外作用的多个重要残基.MCSS计算得到的各种性质官能团在结合腔内的能量优势位置和取向能与已知结合模式的高活性抑制剂的重要基团位置吻合得较好.
Bcl-2 protein is a new target of anticancer drugs with a bright prospect simultaneous search（MCSS） methodology was used to analyze the inhibitors-binding now. The multiple copy site of Bcl-2. The results show＇that the inhibitors-binding site can be divided into five subsites （P1, L1, P2, P3, P4）, the bottom of which is hydrophobic. And several important residues which can form interactions other than hydrophobic interactions distribute on the side and edge of the inhibitors-binding site. Energetically favorable positions and orientations of various functional groups determined by MCSS computing are consistent with these of important groups in high potent inhibitors, which can reversely guide the structure modification and novel design of inhibitors effectively.
出处
《高等学校化学学报》
SCIE
EI
CAS
CSCD
北大核心
2008年第3期591-595,共5页
Chemical Journal of Chinese Universities
基金
第二军医大学博士创新基金(2005年度)
上海市重点学科建设项目(批准号:B906)资助
作者简介
联系人简介：周有骏，男，教授，博士生导师，从事抗真菌和抗肿瘤药物研究．E—mail：zhouyoujun2006@yahoo．com．cn
