基于结构的香农熵及其在金属β-内酰胺酶结构分析中的应用研究

目的:探讨金属β-内酰胺酶残基在结构上的变化程度。方法:对各亚类MBLs结构进行叠合,计算残基间RMSD值,根据RMSD值差异引入基于结构的香农熵,并将基于结构的香农熵映射到1DD6结构上。结果:结构上的变化主要集中在活性位点附近靠外的区域,而活性位点内部则相对变化较小。结论:在活性位点附近loop区残基结构在不同MBLs中变化较大,是决定各亚类MBLs水解活性和特异性的主要因素。这一发现对于指导计算机辅助MBLs抑制剂的设计有着重要的指导作用。

Application of Structure-based Shanon Entropy in Structure Analysis of Metallo-β-lactamase

Objective： To study the variational degree of metallo-β-1actamase（MBLs） residual base in the structure. Methods： The structures of different subclass of MBLs were superposed and the root-meat-square deviations（RMSD） of each amino site were calculated. According to the differences of RMSD value, structure-based Shannon entropy was introduced to reflect the diversity of structure and was mapped to the structure of 1DD6 MBLs. Results： The major vari- ation in the structures focused on the outside area near active site. The structure of inside part of the active site was stable. Conclusion： The structure of the loop region near active site changed greatly in the different MBLs, which were the major factors to determine the hydrolysis activity and specificity of different MBLs. The structure diversity of these residues should be considered when designing broad-spectrum MBLs inhibition.