Arabi Alya A
College of Medicine and Health Sciences, Department of Biochemistry and Molecular Biology, United Arab Emirates University, Al Ain, P.O. Box: 15551, United Arab Emirates.
ACS Omega. 2025 Aug 15;10(33):37462-37473. doi: 10.1021/acsomega.5c03444. eCollection 2025 Aug 26.
A new computational tool, the Average Electron Density Estimator (AED-Est), has been developed along with a new scheme for assigning atom type, the AAA scheme. This combination of the AED-Est and the AAA scheme is designed to rapidly estimate properties, including electron populations, volumes, and average electron density (AED) values, with high precision and an accuracy comparable to values computed at the quantum levels. AED-Est gave comparable results when using three different sets/subsets of various neutral molecules. The AED-Est reference values were obtained using 553 molecules, and then tested on a separate set of 101 molecules. The between the predicted values (obtained via the AED-Est tool) and the actual values (obtained via quantum simulations) reaches 0.99, and the RMSE values are at least 1 order of magnitude smaller than the average values. The new AAA scheme of defining atom types, which can be useful in designing new force fields, can significantly imporve the results compared to the general Amber force field, GAFF2, scheme. The AED-Est tool provided even better predictions of AED values for groups of atoms within a molecule, such as bioisosteric moieties, than for individual atoms. This has significant implications for fields such as drug discovery and the development of more effective therapeutics.
一种新的计算工具——平均电子密度估计器（AED-Est），以及一种新的原子类型分配方案——AAA方案，已经被开发出来。AED-Est和AAA方案的这种结合旨在快速估计各种性质，包括电子布居、体积和平均电子密度（AED）值，具有高精度且其准确度可与量子水平计算得到的值相媲美。当使用各种中性分子的三种不同集合/子集时，AED-Est给出了可比的结果。AED-Est参考值是使用553个分子获得的，然后在另一组101个分子上进行测试。预测值（通过AED-Est工具获得）与实际值（通过量子模拟获得）之间的相关性达到0.99，且均方根误差值比平均值至少小1个数量级。定义原子类型的新AAA方案在设计新的力场时可能会很有用，与通用的Amber力场GAFF2方案相比，它可以显著改善结果。AED-Est工具对于分子内的原子基团（如生物电子等排体部分）的AED值预测，比单个原子的预测效果更好。这对药物发现和开发更有效的治疗方法等领域具有重要意义。
