活性分子对脂质膜穿透性影响的分子动力学仿真
发布时间：2019-06-26 13:33
【摘要】：在生物医学中,通过设计功能性的纳米粒子和优化纳米粒子形状、尺寸和材料特性来提高纳米药物的细胞选择性和绑定效率一直是一个巨大的挑战。纳米药物在目标生物体中的作用过程分为吸附、穿透生物膜和释放药物三个过程。在穿透生物膜的过程中,往往会有一些纳米药物表面的配体(ligand)由于吸附能量问题而停留在生物膜中,这些配体不会随着纳米药物穿透生物膜,而是成为活性分子(Surfactant),停留在生物膜中,从而会影响到脂质生物膜的穿透性,继而影响到纳米药物的吸附及穿透过程。随着计算机技术的高速发展,对很多科学领域产生了深刻的影响。纳米药物的出现给生物医学领域带来了更多的启示和选择,先进的计算机技术被广泛的应用到新药物的开发和药物的优化研究中。本文基于分子动力学原理,应用LAMMPS和Material Studio分子模拟软件,研究了活性剂(Surfactant)对脂质生物膜穿透性的影响。在建模阶段,应用了耗散粒子分子动力学及粗粒化建模技术,通过粗粒化的处理方式,提高了计算的效率和计算时长。本文目标模拟体系由脂质生物膜、流体部分和活性分子组成,其中脂质生物膜由粗粒化的链状结构构成,整个脂质生物膜置于模拟体系的中部,生物膜的上下都充满了粗粒化的水分子,流体部分主要由粗粒化的水分子组成;每次模拟中,脂质生物膜内部将含有不同比例的活性分子,活性分子和脂质生物膜应用简谐势能描述链内相邻原子间的作用力。整个体系应用耗散力分子模拟力场(Dissipative Particle Dynamics)势能进行描述。本文采用粗粒化的分子动力学模拟技术,分析研究了不同含量的活性分子(Surfactant)对脂质生物膜通透性的影响。通过建立含有水、脂质生物膜和活性分子的粗粒化模型,最优化粗粒化模型的结构,得出体系的稳定能量状态;同时,在模拟过程中观察活性剂对脂质生物膜结构稳定性的影响,并计算水分子在每次模拟过程中的聚合分布(concentration profile)和均方位移(MSD)等。通过分析后发现,活性剂的含量增加时,较多的活性分子使原来稳定的脂质生物膜,表现出活性分子的性质,变得不稳定,易于形变和粒子更易于通过;并且,通过对脂质生物膜结构的分析,较高含量的活性剂甚至会破坏脂质生物膜的结构。因此,在研究纳米药物穿透生物膜的过程时,必须考虑停留在脂质生物膜中的活性分子对脂质生物膜穿透性的影响,因为这将影响纳米药物的作用效率。
[Abstract]:In biomedicine, it has been a great challenge to improve the cell selectivity and binding efficiency of nanoparticles by designing functional nanoparticles and optimizing the shape, size and material properties of nanoparticles. The process of nano-drug action in the target organism can be divided into three processes: adsorption, penetration of biofilm and drug release. In the process of penetrating biofilm, some ligands (ligand) on the surface of nano-drug often stay in the biofilm because of the problem of adsorption energy. These ligands do not penetrate the biofilm with nano-drug, but become the active molecule (Surfactant), stays in the biofilm, which will affect the penetration of lipid biofilm, and then affect the adsorption and penetration process of nano-drug. With the rapid development of computer technology, it has a profound impact on many scientific fields. The emergence of nano-drugs has brought more enlightenment and choice to the field of biomedicine. Advanced computer technology has been widely used in the development of new drugs and drug optimization research. Based on the principle of molecular dynamics, the effect of active agent (Surfactant) on the penetration of lipid biofilm was studied by using LAMMPS and Material Studio molecular simulation software. In the modeling stage, the molecular dynamics of dissipative particles and coarse granulation modeling technology are applied to improve the efficiency and time of calculation through the treatment of coarse granulation. In this paper, the target simulation system is composed of lipid biofilm, fluid part and active molecules, in which the lipid biofilm is composed of coarse granulated chain structure, the whole lipid biofilm is placed in the middle of the simulation system, the upper and lower parts of the biofilm are full of coarse granulated water molecules, and the fluid part is mainly composed of coarse granulated water molecules. In each simulation, the lipid biofilm will contain different proportion of active molecules, and the harmonic potential can be used to describe the force between adjacent atoms in the chain. The (Dissipative Particle Dynamics) potential energy of dissipative force molecule simulation force field is used to describe the whole system. In this paper, the effect of different contents of active molecule (Surfactant) on the permeability of lipid biofilm was studied by coarse granulation molecular dynamics simulation technique. Through the establishment of coarse granulation model containing water, lipid biofilm and active molecules, the structure of coarse granulation model was optimized, and the stable energy state of the system was obtained. at the same time, the effect of active agent on the structural stability of lipid biofilm was observed, and the polymerization distribution (concentration profile) and mean square displacement (MSD) of water molecules in each simulation process were calculated. After analysis, it is found that when the content of active agent increases, more active molecules make the original stable lipid biofilm show the properties of active molecules, become unstable, easy to deform and particles easier to pass through, and, through the analysis of the structure of lipid biofilm, the higher content of active agent can even destroy the structure of lipid biofilm. Therefore, in the study of the process of nano-drug penetration into biofilm, it is necessary to consider the effect of active molecules staying in lipid biofilm on the penetration of lipid biofilm, which will affect the efficiency of nano-drug penetration.
【学位授予单位】：电子科技大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R318
本文编号：2506220
[Abstract]:In biomedicine, it has been a great challenge to improve the cell selectivity and binding efficiency of nanoparticles by designing functional nanoparticles and optimizing the shape, size and material properties of nanoparticles. The process of nano-drug action in the target organism can be divided into three processes: adsorption, penetration of biofilm and drug release. In the process of penetrating biofilm, some ligands (ligand) on the surface of nano-drug often stay in the biofilm because of the problem of adsorption energy. These ligands do not penetrate the biofilm with nano-drug, but become the active molecule (Surfactant), stays in the biofilm, which will affect the penetration of lipid biofilm, and then affect the adsorption and penetration process of nano-drug. With the rapid development of computer technology, it has a profound impact on many scientific fields. The emergence of nano-drugs has brought more enlightenment and choice to the field of biomedicine. Advanced computer technology has been widely used in the development of new drugs and drug optimization research. Based on the principle of molecular dynamics, the effect of active agent (Surfactant) on the penetration of lipid biofilm was studied by using LAMMPS and Material Studio molecular simulation software. In the modeling stage, the molecular dynamics of dissipative particles and coarse granulation modeling technology are applied to improve the efficiency and time of calculation through the treatment of coarse granulation. In this paper, the target simulation system is composed of lipid biofilm, fluid part and active molecules, in which the lipid biofilm is composed of coarse granulated chain structure, the whole lipid biofilm is placed in the middle of the simulation system, the upper and lower parts of the biofilm are full of coarse granulated water molecules, and the fluid part is mainly composed of coarse granulated water molecules. In each simulation, the lipid biofilm will contain different proportion of active molecules, and the harmonic potential can be used to describe the force between adjacent atoms in the chain. The (Dissipative Particle Dynamics) potential energy of dissipative force molecule simulation force field is used to describe the whole system. In this paper, the effect of different contents of active molecule (Surfactant) on the permeability of lipid biofilm was studied by coarse granulation molecular dynamics simulation technique. Through the establishment of coarse granulation model containing water, lipid biofilm and active molecules, the structure of coarse granulation model was optimized, and the stable energy state of the system was obtained. at the same time, the effect of active agent on the structural stability of lipid biofilm was observed, and the polymerization distribution (concentration profile) and mean square displacement (MSD) of water molecules in each simulation process were calculated. After analysis, it is found that when the content of active agent increases, more active molecules make the original stable lipid biofilm show the properties of active molecules, become unstable, easy to deform and particles easier to pass through, and, through the analysis of the structure of lipid biofilm, the higher content of active agent can even destroy the structure of lipid biofilm. Therefore, in the study of the process of nano-drug penetration into biofilm, it is necessary to consider the effect of active molecules staying in lipid biofilm on the penetration of lipid biofilm, which will affect the efficiency of nano-drug penetration.
【学位授予单位】：电子科技大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R318
【参考文献】
相关期刊论文 前1条
1 张志勇;尹大川;卢慧甍;;粗粒化模拟及其在生物膜研究领域的应用[J];生命的化学;2010年03期
，本文编号：2506220
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