Huang Wei, Riniker Sereina, van Gunsteren Wilfred F
Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH , 8093 Zürich, Switzerland.
J Chem Theory Comput. 2014 Jun 10;10(6):2213-23. doi: 10.1021/ct500048c.
Molecular dynamics simulation of biomolecules in solvent using an atomic model for both the biomolecules and the solvent molecules is still computationally rather demanding considering the time scale of the biomolecular motions. The use of a supramolecular coarse-grained (CG) model can speed up the simulation considerably, but it also reduces the accuracy inevitably. Combining an atomic fine-grained (FG) level of modeling for the biomolecules and a supramolecular CG level for the solvent into a hybrid system, the increased computational efficiency may outweigh the loss of accuracy with respect to the biomolecular properties in the hybrid FG/CG simulation. Here, a previously published CG methanol model is reparametrized, and then a 1:1 mixture of FG and CG methanol is used to calibrate the FG-CG interactions using thermodynamic and dielectric screening data for liquid methanol. The FG-CG interaction parameter set is applied in hybrid FG/CG solute/solvent simulations of the folding equilibria of three β-peptides that adopt different folds. The properties of the peptides are compared with those obtained in FG solvent simulations and with experimental NMR data. The comparison shows that the folding equilibria in the pure CG solvent simulations are different from those in the FG solvent simulations because of the lack of hydrogen-bonding partners in the supramolecular CG solvent. Next, we introduced an FG methanol layer around the peptides in CG solvent to recover the hydrogen-bonding pattern of the FG solvent simulations. The result shows that with the FG methanol layer, the folding equilibria of the three β-peptides are very similar to those in the FG solvent simulations, while the computational efficiency is at least 3 times higher and the cutoff radius for nonbonded interactions could be increased from 1.4 to 2.0 nm.
考虑到生物分子运动的时间尺度，使用生物分子和溶剂分子的原子模型对溶剂中的生物分子进行分子动力学模拟在计算上仍然要求很高。使用超分子粗粒度（CG）模型可以显著加快模拟速度，但也不可避免地降低了准确性。将生物分子的原子细粒度（FG）建模水平与溶剂的超分子CG水平结合到一个混合系统中，就混合FG/CG模拟中的生物分子特性而言，提高的计算效率可能超过准确性的损失。在这里，对先前发表的CG甲醇模型进行重新参数化，然后使用FG和CG甲醇的1:1混合物，利用液态甲醇的热力学和介电屏蔽数据来校准FG-CG相互作用。FG-CG相互作用参数集应用于三种采用不同折叠方式的β-肽折叠平衡的混合FG/CG溶质/溶剂模拟中。将肽的性质与在FG溶剂模拟中获得的性质以及实验NMR数据进行比较。比较表明，由于超分子CG溶剂中缺乏氢键伙伴，纯CG溶剂模拟中的折叠平衡与FG溶剂模拟中的不同。接下来，我们在CG溶剂中的肽周围引入了一层FG甲醇，以恢复FG溶剂模拟中的氢键模式。结果表明，有了FG甲醇层，三种β-肽的折叠平衡与FG溶剂模拟中的非常相似，而计算效率至少提高了3倍，非键相互作用的截止半径可以从1.4纳米增加到2.0纳米。
