Faculty of Chemical Engineering and Technology, Cracow University of Technology, 24 Warszawska, 31-155, Kraków, Poland.
Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smȩtna, 31-343, Kraków, Poland.
J Mol Model. 2019 Apr 6;25(5):114. doi: 10.1007/s00894-019-3995-6.
The complexes of selected long-chain arylpiperazines with homology models of 5-HT, 5-HT, and 5-HT receptors were investigated using quantum mechanical methods. The molecular geometries of the ligand-receptor complexes were firstly optimized with the Our own N-layered Integrated molecular Orbital and molecular Mechanics (ONIOM) method. Next, the fragment molecular orbitals method with an energy decomposition analysis scheme (FMO-EDA) was employed to estimate the interaction energies in binding sites. The results clearly showed that orthosteric binding sites of studied serotonin receptors have both attractive and repulsive regions. In the case of 5-HT and 5-HT two repulsive areas, located in the lower part of the binding pocket, and one large area of attraction engaging many residues at the top of all helices were identified. Additionally, for the 5-HT receptor, the third area of destabilization located at the extracellular end of the helix 6 was found.
采用量子力学方法研究了选定的长链芳基哌嗪与 5-HT、5-HT 和 5-HT 受体同源模型的配合物。首先使用我们自己的 N 层综合分子轨道和分子力学（ONIOM）方法优化配体-受体配合物的分子几何形状。接下来，采用带有能量分解分析方案的片段分子轨道方法（FMO-EDA）来估算结合部位的相互作用能。结果清楚地表明，研究中血清素受体的正位结合部位既有吸引力区域又有排斥力区域。在 5-HT 和 5-HT 两种情况下，都鉴定到了位于结合口袋下部的两个排斥区域，以及一个位于所有螺旋顶部的包含许多残基的大吸引力区域。此外，对于 5-HT 受体，还在 6 号螺旋细胞外端发现了第三个失稳区域。
