Hazra Milan Kumar, Roy Susmita, Bagchi Biman
Solid State and Structural Chemistry Unit, Indian Institute of Science, Bangalore 560012, India.
J Chem Phys. 2014 Nov 14;141(18):18C501. doi: 10.1063/1.4895539.
As the beneficial effects of curcumin have often been reported to be limited to its small concentrations, we have undertaken a study to find the aggregation properties of curcumin in water by varying the number of monomers. Our molecular dynamics simulation results show that the equilibrated structure is always an aggregated state with remarkable structural rearrangements as we vary the number of curcumin monomers from 4 to 16 monomers. We find that the curcumin monomers form clusters in a very definite pattern where they tend to aggregate both in parallel and anti-parallel orientation of the phenyl rings, often seen in the formation of β-sheet in proteins. A considerable enhancement in the population of parallel alignments is observed with increasing the system size from 12 to 16 curcumin monomers. Due to the prevalence of such parallel alignment for large system size, a more closely packed cluster is formed with maximum number of hydrophobic contacts. We also follow the pathway of cluster growth, in particular the transition from the initial segregated to the final aggregated state. We find the existence of a metastable structural intermediate involving a number of intermediate-sized clusters dispersed in the solution. We have constructed a free energy landscape of aggregation where the metatsable state has been identified. The course of aggregation bears similarity to nucleation and growth in highly metastable state. The final aggregated form remains stable with the total exclusion of water from its sequestered hydrophobic core. We also investigate water structure near the cluster surface along with their orientation. We find that water molecules form a distorted tetrahedral geometry in the 1st solvation layer of the cluster, interacting rather strongly with the hydrophilic groups at the surface of the curcumin. The dynamics of such quasi-bound water molecules near the surface of curcumin cluster is considerably slower than the bulk signifying a restricted motion as often found in protein hydration layer.
由于姜黄素的有益作用通常被报道仅限于其低浓度状态，我们开展了一项研究，通过改变单体数量来探究姜黄素在水中的聚集特性。我们的分子动力学模拟结果表明，当我们将姜黄素单体数量从4个变化到16个时，平衡结构始终是一种具有显著结构重排的聚集态。我们发现姜黄素单体以非常明确的模式形成簇，它们倾向于以苯环的平行和反平行取向聚集，这在蛋白质β-折叠的形成中经常可见。随着系统大小从12个姜黄素单体增加到16个，平行排列的数量显著增加。由于在大系统中这种平行排列占主导，形成了一个具有最大数量疏水接触的更紧密堆积的簇。我们还追踪了簇生长的途径，特别是从初始分离态到最终聚集态的转变。我们发现存在一种亚稳态结构中间体，其中包含一些分散在溶液中的中等大小的簇。我们构建了聚集的自由能景观，其中已识别出亚稳态。聚集过程与高度亚稳态下的成核和生长相似。最终的聚集形式保持稳定，其隔离的疏水核心完全排除了水。我们还研究了簇表面附近的水结构及其取向。我们发现水分子在簇的第一溶剂化层中形成扭曲的四面体几何结构，与姜黄素表面的亲水基团相互作用相当强烈。姜黄素簇表面附近这种准结合水分子的动力学比本体水慢得多，这表明其运动受限，这在蛋白质水化层中经常可见。
