Troitzsch Raphael Z, Tulip Paul R, Crain Jason, Martyna Glenn J
School of Physics, The University of Edinburgh, Edinburgh, United Kingdom.
Biophys J. 2008 Dec;95(11):5014-20. doi: 10.1529/biophysj.108.134916. Epub 2008 Sep 12.
Aqueous proline solutions are deceptively simple as they can take on complex roles such as protein chaperones, cryoprotectants, and hydrotropic agents in biological processes. Here, a molecular level picture of proline/water mixtures is developed. Car-Parrinello ab initio molecular dynamics (CPAIMD) simulations of aqueous proline amino acid at the B-LYP level of theory, performed using IBM's Blue Gene/L supercomputer and massively parallel software, reveal hydrogen-bonding propensities that are at odds with the predictions of the CHARMM22 empirical force field but are in better agreement with results of recent neutron diffraction experiments. In general, the CPAIMD (B-LYP) simulations predict a simplified structural model of proline/water mixtures consisting of fewer distinct local motifs. Comparisons of simulation results to experiment are made by direct evaluation of the neutron static structure factor S(Q) from CPAIMD (B-LYP) trajectories as well as to the results of the empirical potential structure refinement reverse Monte Carlo procedure applied to the neutron data.
脯氨酸水溶液看似简单，实则不然，因为它们在生物过程中可发挥多种复杂作用，如充当蛋白质伴侣、冷冻保护剂和助水溶试剂。在此，构建了脯氨酸/水混合物的分子水平图景。使用IBM的蓝色基因/L超级计算机和大规模并行软件，在B-LYP理论水平上对脯氨酸氨基酸水溶液进行了Car-Parrinello从头算分子动力学（CPAIMD）模拟，结果揭示出的氢键倾向与CHARMM22经验力场的预测不一致，但与近期中子衍射实验的结果更相符。总体而言，CPAIMD（B-LYP）模拟预测了脯氨酸/水混合物的简化结构模型，该模型包含的不同局部基序较少。通过直接评估CPAIMD（B-LYP）轨迹中的中子静态结构因子S(Q)，以及将经验势结构精修反向蒙特卡罗程序应用于中子数据的结果，将模拟结果与实验进行了比较。
