FORCE-FIELD DESIGN FOR METALLOPROTEINS
FORCE-FIELD DESIGN FOR METALLOPROTEINS
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DOI：
10.1021/ja00022a010
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发表时间：
1991-10-23
影响因子：
15
通讯作者：
MERZ, KM
中科院分区：
文献类型：
--
作者：
HOOPS, SC;ANDERSON, KW;MERZ, KM
在这里，我们描述了一个一般的方法来系统推导力场参数的金属蛋白。特别是，我们已经扩展了琥珀力场模拟锌离子在人类碳酸酐酶II（HCAII）在高（锌氢氧化物）和低（锌水）pH值的形式。这种方法的关键要素是系统评价的分子轨道方法建模的金属中心（锌在HCAII）与其配体在活性位点和力场表示的静电相互作用与点电荷适合的静电势。嵌入在蛋白质环境中的活性位点的静电相互作用建模的精度更高，增加了研究人类碳酸酐酶II的静态和动态结构的能力。这种方法应该是转移到其他金属蛋白质在固定的配位数的计算研究。
Herein we describe a general approach to systematic derivation of force field parameters for metalloproteins. In particular, we have extended the AMBER force field to model the zinc ion in human carbonic anhydrase II (HCAII) in both the high (zinc-hydroxide) and low (zinc-water) pH forms. Key elements of this approach are the systematic evaluation of molecular orbital methods for modeling the metallic center (zinc in HCAII) with its ligands in the active site and the force field representation of electrostatic interactions with point charges fitted to the electrostatic potential. The resulting greater accuracy in modeling electrostatic interactions for the active site embedded in the protein environment increases the capacity for studying the static and dynamic structure of human carbonic anhydrase II. This approach should be transferable to computational studies of other metalloproteins at fixed coordination numbers.