New Delhi metallo - beta - lactamase - 1 ( NDM - 1 ) is an enzyme that makes bacteria resistant to a broad range of antibiotics of beta - lactam category. By apply computation biology, through molecular modeling, the multiple lactamase enzymatic activities are compared and analyzed, so as to provide theoretical guideline in new drug discovery approaches against the NDM - 1 containing superbugs. NDM -1 sequences were used to blast the protein database, so as to retrieve sequences with relevant homology. Multiple sequences were selected based on similarity in the molecular modeling procedures. Since the crystal structure of the VIM -2 is available, the molecular modeled NDM -1 was aligned with the active motif of the VIM - 2 structure. The analysis has demonstrated that NDM - 1 exhibits the greatest similarity in several critical amino acid residues that bind zinc ions. Some uniqueness in the amino acids also existed though. The 3-D structures in VIM - 2 and NDM - 1 also showed great resemblance. The enhanced enzymatic activities of the NDM - 1, might because the demonstrated uniqueness of the ami-no acid residues around the enzymatic motif. The uniqueness of the amino acids change the conformation of the active domain, hence increased the beta - lactamase activity.%近期研究发现的超级病原菌耐药的原因,是其含有一种特殊的金属内酰胺酶-NDM -1.采用计算生物学技术,通过分子建模、使NDM -1与其它金属B-内酰胺酶类相比对,探索NDM -1对于β-内酰胺类抗生素具有广谱的水解能力的分子机理,为相关新药的开发提供理论依据.将NDM -1序列用BLAST进行同源性搜索,挑选一些相似性较高的序列进行多序列比对的同源建模,对所得的模型进行评估.根据已知的VIM -2晶体结构,使计算的NDM -1模型活性位点与已知VIM -2金属酶结构进行比较分析；结果发现NDM -1在锌离子结合位点的几个关键的氨基酸残基,与VIM -2金属酶较为相似.同对活性位点附近的氨基酸残基的立体折叠结构也与VIM -2存在相似性.NDM -1水解谱的广泛性,可能在于活性位点附近一些氨基酸残基的差异,后者可通过改变空间结构,从而增加了 NDM -1的水解活性.
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