Laboratório de Química Computacional, LQC, Universidade de Brasília, Instituto de Química, Brasília, DF, Brazil.
J Mol Model. 2011 Jun;17(6):1371-9. doi: 10.1007/s00894-010-0838-x. Epub 2010 Sep 14.
Hartree-Fock and density functional methods were used to analyze electronic and structural properties of known drugs to evaluate the influence of these data on acetylcholinesterase inhibition. The energies of the frontier orbitals and the distances between the more acidic hydrogen species were investigated to determine their contributions to the activity of a group of acetylcholinesterase inhibitors. Electrostatic potential maps indicated suitable sites for drugs-enzyme interactions. In this study, the structural, electronic and spatial properties of nine drugs with known inhibitory effects on acetylcholinesterase were examined. The data were obtained based on calculations at the B3LYP/6-31 + G(d,p) level. Multivariate principal components analysis was applied to 18 parameters to determine the pharmacophoric profile of acetylcholinesterase inhibitors. Desirable features for acetylcholinesterase inhibitor molecules include aromatic systems or groups that simulate the surface electrostatic potential of aromatic systems and the presence of a sufficient number of hydrogen acceptors and few hydrogen donors. PCA showed that electronic properties, including the HOMO-1 orbital energy, logP and aromatic system quantity, as well as structural data, such as volume, size and H-H distance, are the most significant properties.
采用 Hartree-Fock 和密度泛函方法分析了已知药物的电子和结构性质，以评估这些数据对乙酰胆碱酯酶抑制的影响。研究了前线轨道的能量和更酸性氢物种之间的距离，以确定它们对一组乙酰胆碱酯酶抑制剂活性的贡献。静电势图表明了适合药物-酶相互作用的部位。在这项研究中，检查了九种具有已知乙酰胆碱酯酶抑制作用的药物的结构、电子和空间性质。这些数据是基于 B3LYP/6-31 + G(d,p) 水平的计算获得的。应用多元主成分分析对 18 个参数进行了分析，以确定乙酰胆碱酯酶抑制剂的药效团特征。乙酰胆碱酯酶抑制剂分子的理想特征包括模拟芳香系统表面静电势的芳香系统或基团，以及存在足够数量的氢键受体和较少的氢键供体。PCA 表明，电子性质，包括 HOMO-1 轨道能量、logP 和芳香系统数量，以及结构数据，如体积、大小和 H-H 距离，是最重要的性质。
