Laboratory of Molecular Modeling Applied to Chemical and Biological Defense, Military Institute of Engineering, Rio de Janeiro, Brazil; Department of Chemistry, Faculty of Science, University of Hradec Kralove, Rokitanskeho 62, 50003, Hradec Kralove, Czech Republic.
Laboratory of Molecular Modeling Applied to Chemical and Biological Defense, Military Institute of Engineering, Rio de Janeiro, Brazil.
Chem Biol Interact. 2023 Sep 1;382:110619. doi: 10.1016/j.cbi.2023.110619. Epub 2023 Jul 3.
The Near Attack Conformation (NAC) approach states that the efficiency of an enzyme-catalyzed reaction depends on the prior attainment of optimal conditions for substrate atom organization and positioning for bond formation. These conditions are prerequisites for the transition state (TS) in which the involved atoms are within the van der Waals range of contact and positioned at an angle similar to that achieved after bond formation. The successful application of this approach to investigate the reactivation mechanism of acetylcholinesterase inhibited by nerve agents has contributed to a better understanding of this mechanism and demonstrated consistent corroboration with experimental data. In this article, we summarize the accomplishments achieved thus far and outline future perspectives.
近攻击构象（NAC）方法指出，酶催化反应的效率取决于底物原子组织和键形成位置的最佳条件的预先实现。这些条件是过渡态（TS）的前提，其中涉及的原子在范德华接触范围内，并以类似于键形成后达到的角度定位。该方法成功应用于研究受神经毒剂抑制的乙酰胆碱酯酶的重激活机制，有助于更好地理解该机制，并与实验数据一致。在本文中，我们总结了迄今为止取得的成就，并概述了未来的展望。
