活性分子對脂質膜穿透性影響的分子動力學仿真
發(fā)布時間：2019-06-26 13:33
【摘要】：在生物醫(yī)學中,通過設計功能性的納米粒子和優(yōu)化納米粒子形狀、尺寸和材料特性來提高納米藥物的細胞選擇性和綁定效率一直是一個巨大的挑戰(zhàn)。納米藥物在目標生物體中的作用過程分為吸附、穿透生物膜和釋放藥物三個過程。在穿透生物膜的過程中,往往會有一些納米藥物表面的配體(ligand)由于吸附能量問題而停留在生物膜中,這些配體不會隨著納米藥物穿透生物膜,而是成為活性分子(Surfactant),停留在生物膜中,從而會影響到脂質生物膜的穿透性,繼而影響到納米藥物的吸附及穿透過程。隨著計算機技術的高速發(fā)展,對很多科學領域產生了深刻的影響。納米藥物的出現(xiàn)給生物醫(yī)學領域帶來了更多的啟示和選擇,先進的計算機技術被廣泛的應用到新藥物的開發(fā)和藥物的優(yōu)化研究中。本文基于分子動力學原理,應用LAMMPS和Material Studio分子模擬軟件,研究了活性劑(Surfactant)對脂質生物膜穿透性的影響。在建模階段,應用了耗散粒子分子動力學及粗粒化建模技術,通過粗�；奶幚矸绞�,提高了計算的效率和計算時長。本文目標模擬體系由脂質生物膜、流體部分和活性分子組成,其中脂質生物膜由粗粒化的鏈狀結構構成,整個脂質生物膜置于模擬體系的中部,生物膜的上下都充滿了粗�；乃肿�,流體部分主要由粗�；乃肿咏M成;每次模擬中,脂質生物膜內部將含有不同比例的活性分子,活性分子和脂質生物膜應用簡諧勢能描述鏈內相鄰原子間的作用力。整個體系應用耗散力分子模擬力場(Dissipative Particle Dynamics)勢能進行描述。本文采用粗�；姆肿觿恿W模擬技術,分析研究了不同含量的活性分子(Surfactant)對脂質生物膜通透性的影響。通過建立含有水、脂質生物膜和活性分子的粗�；Ｐ�,最優(yōu)化粗粒化模型的結構,得出體系的穩(wěn)定能量狀態(tài);同時,在模擬過程中觀察活性劑對脂質生物膜結構穩(wěn)定性的影響,并計算水分子在每次模擬過程中的聚合分布(concentration profile)和均方位移(MSD)等。通過分析后發(fā)現(xiàn),活性劑的含量增加時,較多的活性分子使原來穩(wěn)定的脂質生物膜,表現(xiàn)出活性分子的性質,變得不穩(wěn)定,易于形變和粒子更易于通過;并且,通過對脂質生物膜結構的分析,較高含量的活性劑甚至會破壞脂質生物膜的結構。因此,在研究納米藥物穿透生物膜的過程時,必須考慮停留在脂質生物膜中的活性分子對脂質生物膜穿透性的影響,因為這將影響納米藥物的作用效率。
[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.
【學位授予單位】：電子科技大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R318
本文編號：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.
【學位授予單位】：電子科技大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R318
【參考文獻】
相關期刊論文 前1條
1 張志勇;尹大川;盧慧甍;;粗粒化模擬及其在生物膜研究領域的應用[J];生命的化學;2010年03期
，本文編號：2506220
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