Department of Biological Sciences and Bioengineering, Lehigh University, 111 Research Dr. Bethlehem, Pennsylvania 18015.
Department of Chemistry, Lehigh University, 6 E. Packer Ave. Bethlehem, Pennsylvania 18015.
J Comput Chem. 2019 Jun 15;40(16):1570-1577. doi: 10.1002/jcc.25807. Epub 2019 Mar 3.
The structure and dynamics of a truncated (residues 82-136) caveolin-1 (Cav1) construct having a helix-break-helix motif are explored by both all-atom free energy and molecular dynamics (MD) simulations in an explicit bilayer membrane. Two stable Cav1 conformations with small (LB-Cav1) and large hinge angles (RB-Cav1) between two helices are identified although their relative free energy cannot be reliably estimated due to the sampling issues. RB-Cav1s contain one or two lipids residing between the helices that are hydrogen bonded (h-bonded) to both helices in a multidentate fashion. LB-Cav1s show the helices with mono-dentate lipid h-bond interactions or multidentate interactions limited to a single helix at most. The two conformational states of Cav1 remain their initial state during 2-μs MD simulation, suggesting that there is a significant hidden barrier (other than the insertion depth of Cav1 and its hinge angle) and the Cav1 conformational states are tightly regulated by the h-bonds between Cav1 and lipids along with the associated lipid rearrangement during the course of Cav1 conformational changes. © 2019 Wiley Periodicals, Inc.
使用全原子自由能和分子动力学（MD）模拟在明确定义的双层膜中探索具有螺旋断裂螺旋基序的截断（残基 82-136）窖蛋白-1（Cav1）结构的结构和动力学。尽管由于采样问题无法可靠估计其相对自由能，但确定了两个稳定的 Cav1 构象，其两个螺旋之间的小（LB-Cav1）和大铰链角度（RB-Cav1）。RB-Cav1 包含一个或两个位于螺旋之间的脂质，这些脂质以多齿方式与两个螺旋氢键（h-bonded）。LB-Cav1 显示出具有单齿脂质 h-bond 相互作用或最多仅限于一个螺旋的多齿相互作用。在 2-μs MD 模拟过程中，Cav1 的两种构象状态保持其初始状态，这表明存在显著的隐藏障碍（除了 Cav1 的插入深度和其铰链角度之外），并且 Cav1 的构象状态受到 Cav1 和脂质之间的氢键以及相关脂质在 Cav1 构象变化过程中的重排的紧密调节。©2019Wiley Periodicals，Inc.
