Panahi Afra, Feig Michael
Department of Chemistry, Michigan State University, East Lansing, MI, 48824.
J Chem Theory Comput. 2013 Mar 12;9(3):1709-1719. doi: 10.1021/ct300975k.
An extension to the heterogeneous dielectric generalized Born (HDGB) implicit membrane formalism is presented to allow dynamic membrane deformations in response to membrane-inserted biomolecules during molecular dynamic simulations. The flexible membrane is implemented through additional degrees of freedom that represent the membrane deformation at the contact points of a membrane-inserted solute with the membrane. The extra degrees of freedom determine the dielectric and non-polar solvation free energy profiles that are used to obtain the solvation free energy in the presence of the membrane and are used to calculate membrane deformation free energies according to an elastic membrane model. With the dynamic HDGB (DHDGB) model the membrane is able to deform in response to the insertion of charged molecules thereby avoiding the overestimation of insertion free energies with static membrane models. The DHDGB model also allows the membrane to respond to the insertion of membrane-spanning solutes with hydrophobic mismatch. The model is tested with the membrane insertion of amino acid side chain analogs, arginine-containing helices, the WALP23 peptide, and the gramicidin A channel.
本文提出了一种对异质介电广义玻恩（HDGB）隐式膜形式主义的扩展，以便在分子动力学模拟期间允许膜响应插入膜中的生物分子而发生动态变形。通过额外的自由度来实现柔性膜，这些自由度表示插入膜中的溶质与膜的接触点处的膜变形。这些额外的自由度确定了介电和非极性溶剂化自由能分布，用于在存在膜的情况下获得溶剂化自由能，并根据弹性膜模型用于计算膜变形自由能。使用动态HDGB（DHDGB）模型，膜能够响应带电分子的插入而变形，从而避免了静态膜模型对插入自由能的高估。DHDGB模型还允许膜响应具有疏水错配的跨膜溶质的插入。该模型通过氨基酸侧链类似物、含精氨酸的螺旋、WALP23肽和短杆菌肽A通道的膜插入进行了测试。
