Department of Pharmaceutical and Medicinal Chemistry, Faculty of Chemistry and Pharmacy, University of Regensburg, Universitätsstrasse 31, Regensburg, Germany.
J Mol Model. 2010 Aug;16(8):1307-18. doi: 10.1007/s00894-010-0646-3. Epub 2010 Jan 30.
The aim of this study was to perform an in silico analysis of the interaction of the human beta(2) adrenergic receptor with Galpha(s). In a first step, a systematic surface-interaction-scan between the inactive or active human beta(2) adrenergic receptor and Galpha(s) was performed in order to gain knowledge about energetically preferred areas on the potential energy surface. Subsequently, two energetically favored regions for the active human beta(2) adrenergic receptor-Galpha(s) complex were identified. Two representative complex structures were put into a POPC (1-palmitoyl-2-oleoyl-phosphatidylcholine) bilayer and solvated in order to perform molecular dynamic simulations. The simulations revealed that both conformations, which have comparable potential energy, are stable. A mean number of about 14 hydrogen bonds was observed between the active receptor and Galpha(s) for both conformations. Based on these results, two energetically favored beta(2)-Galpha(s)complexes can be proposed.
本研究旨在对人β2 肾上腺素能受体与 Galpha(s) 的相互作用进行计算机模拟分析。在第一步中，我们对失活或激活的人β2 肾上腺素能受体与 Galpha(s) 之间进行了系统的表面相互作用扫描，以便了解潜在能量表面上能量优先的区域。随后，确定了两种有利于人β2 肾上腺素能受体-Galpha(s) 复合物的能量有利区域。选择两个有代表性的复合物结构放入 1-棕榈酰-2-油酰基-磷酸胆碱（POPC）双层中并进行溶剂化处理，以进行分子动力学模拟。模拟结果表明，两种构象的势能相当，均具有稳定性。对于两种构象，观察到活性受体与 Galpha(s) 之间存在约 14 个氢键。基于这些结果，可以提出两种有利于能量的β2-Galpha(s) 复合物。
