在理論和模擬不同種的實驗方法下,水溶液中離子與離子對的水合結構、水合能、分子動態學是一個長期研究且具吸引力的主題，值得一提的是鈣離子在生物系統上扮演極具影響的角色，另一方面在各組研究顯示鈣離子與水的配位的結果是不一致的。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的方法來估算陽離子與陰離子的蘭納-瓊斯作用力，此近似的方法使用在系統預設值來進行分子動態模擬產生陽、陰離子相互作用力是不當的。 此次的研究，我們採用Luo與Roux所提出的方法來改善鈣離子與氯離子及醋酸根上氧原子的蘭納-瓊斯作用參數，有兩組力場參數需要進行優化，第一組為CHARMM預設參數的鈣離子與氯離子以及鈣離子與醋酸根上氧原子的蘭納-瓊斯作用參數(鈣與水形成五角雙錐體)第二組Lim的參數(鈣與水形成四角反稜柱)。基於使用Lim的鈣離子蘭納-瓊斯參數下，來修正鈣離子與氯離子和醋酸根上氧原子的蘭納-瓊斯作用力，我們模擬結果發現優化後的Lim參數可以重現在近乎飽和濃度下的滲透壓實驗值且鈣離子與氯離子蘭納-瓊斯作用參數還能重現大範圍滲透壓的結果，但在CHARMM預設下鈣離子與氯離子和醋酸根上氧原子的蘭納-瓊斯作用參數卻是辦不到的，並且使用Lim的鈣離子與醋酸根上氧原子的蘭納-瓊斯作用參數在鈣結和蛋白質的模擬上不僅可以符合X-ray結構下的結合點位，同時也擁有著可以接受的鈣氧結合距離，再者，使用我們優化後的Lim鈣離子與氯離子/醋酸根上氧原子蘭納-瓊斯作用力的結果還能支持近期鈣離子與水配位為八的結果，且改善方法容易操作在CHARMM與NAMD的軟體中。 ;Local hydrated structure, molecular dynamics, and hydration energies of ions and ion-pairs in aqueous solution have long been an attractive topic under investigated in terms of various experimental, theoretical, and simulation methods. Especially, Calcium ions (Ca2+) play an important role in mediating and regulating biological systems. Experimental and simulation results regarding the Ca2+H2O coordination number are pretty diverse. 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) interacting parameters, 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 Roux1 to determine the Ca2+Cl and Ca2+OAcLJ interaction parameter. Two sets of Ca2+ LJ parameters are used for optimization: CHARMM36 and Lim’s parameters. Based on the Lim’s Ca2+ LJ parameters, the Ca2+Cl and Ca2+oxygen atom of OAc LJ interaction parameter are able to be optimized to reproduce experimentally-measured osmotic pressure at nearly saturated concentration, whereas CHARMM36 Ca2+ LJ parameters are not. Using the optimized Ca2+Cl/Ca2+oxygen atom of OAc LJ interaction parameter, the osmotic pressures of CaCl2 solution at a wide range of concentration and the osmotic pressures of Ca(OAc)2 solution at a saturated concentration are well reproduced. Furthermore, it gives a concentration-independent Ca2+H2O coordination number of 8, which is consistent with the recently experimental results. Using our optimized Ca2+oxygen atom of OAc LJ interaction parameters, we are able to reproduce the structure of x-ray crystallographically determined proteinCa2+ binding sites. Our results can be simply implemented in CHARMM and NAMD softwares for further biomolecule simulations.
