在計算模擬實驗中，離子可利用於多樣的生物系統之中，因此離子在水溶液中時，各項數據準確度是非常重要的。值得一提的是鈣離子與鎂離子在細胞膜生理功能上扮演極具影響的角色。早前的古典力場分子模擬研究指出高濃度電解液中會觀察到過多離子簇生成，其原因來自於使用Lorentz-Berthelot combining rule的方法估算陽離子與陰離子的蘭納-瓊斯作用力，此估算方法使用在系統預設值來進行分子動態模擬產生出的陽、陰離子相互作用力與實際狀況是有誤差的。 此次的研究，我們採用Luo與 Roux所提出的方法來改善鎂離子與氯離子、醋酸根離子上的氧原子之間的蘭納-瓊斯作用力參數，有兩組力場參數需要進行優化，第一組為CHARMM36預設的鎂離子與氯離子、醋酸根離子上的氧原子之間的蘭納-瓊斯作用力參數， 第二組則為Lim的鎂離子參數。模擬結果發現在氯化鎂溶液系統中兩種參數可以重現在高濃度下的滲透壓實驗值且鎂離子與氯離子蘭納-瓊斯作用參數改進後還能重現大範圍濃度滲透壓的結果 。同樣地，利用CHARMM36力場參數的鎂離子與醋酸根離子蘭納-瓊斯作用力參數改進也可沿用上述方法，並利用修正後的參數來模擬與鎂離子鍵結的蛋白質以測試其正確性。然而我們發現到鎂離子與氯離子、醋酸根離子上的氧原子之間作用力參數優化過長的現象，可能的原因為其緩慢的水交換速率。實驗測得鎂離子的水交換率高達〜1s，這表明我們的模擬時間太短而無法達到熱平衡。 ;An accurate potential function of ion solvation in aqueous solution is crucial for computer simulations of various biological systems. Previous studies have shown that the excess ion cluster formation in concentrated electrolyte solutions observed in classical molecular dynamics simulations (MD) is arisen from the improper cation-anion Lennard-Jones (LJ) interaction parameters, commonly approximated by Lorentz-Berthelot combining rule, which are generally default used in MD simulations. In this study, we follow the same methodology proposed by Luo and Roux to determine the Mg2+Cl and Mg2+O atom of OAcLJ interaction parameter. Two sets of Mg2+ LJ parameters are used for optimization: default CHARMM36 and Lim’s parameters. The two sets of Mg2+Cl LJ interaction parameters are able to be optimized to reproduce experimentally-measured osmotic pressure at high concentration. Using the optimized Mg2+Cl LJ interaction parameter, the osmotic pressures at a wide range of MgCl2 concentration are well reproduced. Similarly, the Mg2+oxygen atom of OAc interaction LJ parameter based on CHARMM36 FF can be optimized. Nevertheless, the Rmin values are too large to be applied widely. We ascribe the bottleneck of Mg2+ solution simulations as well as its parameter optimization to its slow water exchange rate. The experimentally-measured water exchange rate of Mg2+ is up to ~1 s indicated that our simulations are obviously too short to reach thermal equilibrium.
