Abstract

Three-dimensional full-atom model of the enzyme complex with acetyl-CoA and substrate was constructed on the basis of the primary sequence of amino acid residues of N-acetyl glutamate synthase. Bioinformatics approaches of computer modeling were applied, including multiple sequence alignment, prediction of co-evolutionary contacts, and ab initio folding. On the basis of the results of calculations by classical molecular dynamics and combined quantum and molecular mechanics (QM/MM) methods, the structure of the active site and the reaction mechanism of N-acetylglutamate formation are described. Agreement of the structures of the enzyme–product complexes obtained in computer modeling and in the X-ray studies validates the reliability of modeling predictions.

中文翻译：

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N-乙酰谷氨酸合酶的计算机建模：从一级结构到催化的基本阶段

摘要

基于N-乙酰谷氨酸合酶氨基酸残基的一级序列，构建了具有乙酰辅酶A和底物的酶复合物的三维全原子模型。应用了计算机建模的生物信息学方法，包括多序列比对，共同进化联系的预测和从头算起的折叠。根据经典分子动力学和量子分子力学（QM / MM）方法的计算结果，描述了N-乙酰谷氨酸形成的活性位点的结构和反应机理。通过计算机建模和X射线研究获得的酶产物复合物的结构一致，验证了建模预测的可靠性。