• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>Springer Open Choice >A method for predicting individual residue contributions to enzyme specificity and binding-site energies and its application to MTH1
【2h】

A method for predicting individual residue contributions to enzyme specificity and binding-site energies and its application to MTH1

机译：预测单个残基对酶特异性和结合位点能量的贡献的方法及其在MTH1中的应用

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A new method for predicting the energy contributions to substrate binding and to specificity has been developed. Conventional global optimization methods do not permit the subtle effects responsible for these properties to be modeled with sufficient precision to allow confidence to be placed in the results, but by making simple alterations to the model, the precisions of the various energies involved can be improved from about ±2 kcal mol−1 to ±0.1 kcal mol−1. This technique was applied to the oxidized nucleotide pyrophosphohydrolase enzyme MTH1. MTH1 is unusual in that the binding and reaction sites are well separated—an advantage from a computational chemistry perspective, as it allows the energetics involved in docking to be modeled without the need to consider any issues relating to reaction mechanisms. In this study, two types of energy terms were investigated: the noncovalent interactions between the binding site and the substrate, and those responsible for discriminating between the oxidized nucleotide 8-oxo-dGTP and the normal dGTP. Both of these were investigated using the semiempirical method PM7 in the program MOPAC. The contributions of the individual residues to both the binding energy and the specificity of MTH1 were calculated by simulating the effect of mutations. Where comparisons were possible, all calculated results were in agreement with experimental observations. This technique provides fresh insight into the binding mechanism that enzymes use for discriminating between possible substrates.
机译：已经开发了一种预测能量对底物结合和特异性贡献的新方法。常规的全局优化方法不允许以足够的精度对负责这些属性的微妙效果进行建模，以使结果具有置信度，但是通过对模型进行简单的更改，可以提高所涉及各种能量的精度。约±2 kcal mol -1 至±0.1 kcal mol -1 。将该技术应用于氧化的核苷酸焦磷酸水解酶MTH1。 MTH1之所以与众不同，是因为结合位点和反应位点被很好地分开了-从计算化学的角度来看，这是一个优势，因为它允许对接中涉及的能量进行建模，而无需考虑与反应机理有关的任何问题。在这项研究中，研究了两种类型的能量项：结合位点和底物之间的非共价相互作用，以及负责区分氧化的核苷酸8-oxo-dGTP和正常dGTP的那些。在程序MOPAC中使用半经验方法PM7对这两种方法进行了研究。通过模拟突变的影响来计算单个残基对结合能和MTH1特异性的贡献。如果可能进行比较，则所有计算结果均与实验观察结果一致。该技术为酶用于区分可能的底物的结合机制提供了新的见解。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号