Li Xianfeng, Murthy N Sanjeeva, Becker Matthew L, Latour Robert A
Department of Bioengineering, Clemson University, Clemson, South Carolina 29634.
New Jersey Center for Biomaterials, Rutgers University, Piscataway, New Jersey 08854.
Biointerphases. 2016 Jun 24;11(2):021002. doi: 10.1116/1.4944829.
A multiscale modeling approach is presented for the efficient construction of an equilibrated all-atom model of a cross-linked poly(ethylene glycol) (PEG)-based hydrogel using the all-atom polymer consistent force field (PCFF). The final equilibrated all-atom model was built with a systematic simulation toolset consisting of three consecutive parts: (1) building a global cross-linked PEG-chain network at experimentally determined cross-link density using an on-lattice Monte Carlo method based on the bond fluctuation model, (2) recovering the local molecular structure of the network by transitioning from the lattice model to an off-lattice coarse-grained (CG) model parameterized from PCFF, followed by equilibration using high performance molecular dynamics methods, and (3) recovering the atomistic structure of the network by reverse mapping from the equilibrated CG structure, hydrating the structure with explicitly represented water, followed by final equilibration using PCFF parameterization. The developed three-stage modeling approach has application to a wide range of other complex macromolecular hydrogel systems, including the integration of peptide, protein, and/or drug molecules as side-chains within the hydrogel network for the incorporation of bioactivity for tissue engineering, regenerative medicine, and drug delivery applications.
提出了一种多尺度建模方法，用于使用全原子聚合物一致力场（PCFF）高效构建基于交联聚乙二醇（PEG）的水凝胶的平衡全原子模型。最终的平衡全原子模型是通过一个系统的模拟工具集构建的，该工具集由三个连续部分组成：（1）使用基于键涨落模型的晶格蒙特卡罗方法，以实验确定的交联密度构建全局交联PEG链网络；（2）通过从晶格模型过渡到基于PCFF参数化的非晶格粗粒度（CG）模型来恢复网络的局部分子结构，然后使用高性能分子动力学方法进行平衡；（3）通过从平衡的CG结构反向映射来恢复网络的原子结构，用明确表示的水使结构水合，然后使用PCFF参数化进行最终平衡。所开发的三阶段建模方法适用于广泛的其他复杂大分子水凝胶系统，包括将肽、蛋白质和/或药物分子作为侧链整合到水凝胶网络中，以纳入用于组织工程、再生医学和药物递送应用的生物活性。
