三聚体纳米颗粒自组装过程的分子动力学模拟

为了更深入理解直链淀粉/β-乳球蛋白/α-亚油酸三元复合物体系自组装行为的机制,该研究借助Gromacs软件,采用分子动力学模拟对玉米直链淀粉、β-乳球蛋白、α-亚油酸三者在373 K温度下的结合过程进行研究。通过三元纳米粒子在500 ns内的自组装快照图,可以得出直链淀粉、α-亚油酸、β-乳球蛋白3种组分的结合顺序。通过三元纳米粒子的自由能曲面图,可知该三元纳米粒子的形成是热力学自发的过程。进一步对其水合半径及溶剂可接触表面积的分析表明,该三元复合物纳米颗粒溶解性良好。研究阐释了水溶性自组装纳米颗粒的形成机理,为纳米科学领域寻找合适的壁材提供了一种新的研究途径。

Molecular dynamics simulation of self-assembling process of ternary nanoparticle

Ternary complex system of amylose/whey protein/free fatty acid has attracted significant interest in food nutraceuticals or functional compounds in food delivery systems due to the well-known low toxicity,excellent biocompatibility,and solubility.Maize amylose,β-lactoglobulin,α-linoleic acid were self-assembled and characterized by the TEM.Then,in order to understand the mechanism of the self-assembling actions of such a ternary system (interaction among amylose,β-lactoglobulin and α-linoleic acid) deeply,all-atom molecular dynamics simulations were performed to analyze the self-assembling of the 3 components by the Gromacs software.An amylose segment of 55 glucose residues was used to form a 6-fold left-handed helix with 55 nm inner diameter and 135 nm outer diameter approximately and a length of 738 nm.A β-lactoglobulin peptide segment was used on the basis of the three-dimensional (3D) structure determined from an NMR (nuclear magnetic resonance) analysis.The PDB (protein data bank) file for α-linoleic acid was obtained from the Heterocompound Information Centre in Uppsala,Sweden.The glucose force field was chosen and all simulations for the amylose-like molecule were carried out using the glucose force field.The Gromacs 4.6.1 MD package (ScalaLife Competence Center,European Research Council) was used for the simulation.The MD simulations were performed using the leapfrog motion routine with a 2× 10-15 s time step.A total of 250 000 000 simulation steps (for a total of 500 ns simulation time) were performed to assess the progression of the self-assembly process.The LINCS algorithm was used to constrain all bond lengths.In the simulation,the temperature was set at 100 ℃,necessary for the initial formation of the nanoparticle.This was performed using the modified Berendsen thermocouple between the different groups with a relaxation time of 0.1 ps,and the pressure was maintained at 1.0× 105 Pa using the Parrinello-Rahman coupling to a pressure bath via an isotropic coordinate scaling with a relaxation time of 2× 10-12 s.Non-chemical bond interactions were handled using a neighboring grid cell cutoff scheme.Within a neighboring molecules list's cutoff distance of 0.9 nm in a short range,the interactions were evaluated at every time step based on a pair list.A short-range electrostatic cutoff radius of 0.9 nm and a long-range Van der Waals' cutoff radius of 1.4 nm were evaluated simultaneously with each list updating.The binding order of the 3 components could be obtained through the self-assembly snapshot diagram of ternary nanoparticles within 500 ns.The TEM images showed that ternary nanoparticles had a rod-like conformation,which could be confirmed by the snapshot at 500 ns of ternary system from molecular dynamic simulation.Further analyses of their gyration radius and solvent accessible surface area showed that the ternary nanoparticles were highly hydrosoluble,which indicated that the nanoparticles could significantly enhance the aqueous solubility of some hydrophobic nutraceuticals or functional compounds.It also indicated that the formation of the ternary nanoparticles was a thermodynamically spontaneous process among amylose,β-lactoglobulin and α-linoleic acid interaction through the free energy curved-surface map of the ternary nanoparticle.The present work provides insights into the mechanism of the atomic structures of aqueous soluble self-assembled nanoparticles and presents new perspective for the design of nutraceuticals delivery systems with desirable properties.