Molecular dynamics simulations on the interactions between nucleic acids and a phospholipid bilayer

doi:10.1088/1674-1056/ad1178

中国物理B ›› 2024, Vol. 33 ›› Issue (2): 28701-028701.doi: 10.1088/1674-1056/ad1178

Molecular dynamics simulations on the interactions between nucleic acids and a phospholipid bilayer

Yao Xu(徐耀)¹, Shu-Wei Huang(黄舒伟)¹, Hong-Ming Ding(丁泓铭)^2,†, and Yu-Qiang Ma(马余强)¹

1 National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China;
2 Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou 215006, China

收稿日期:2023-10-02 修回日期:2023-11-10 接受日期:2023-12-01 出版日期:2024-01-16 发布日期:2024-01-16
通讯作者: Hong-Ming Ding E-mail:dinghm@suda.edu.cn
基金资助:
Project supported by the National Natural Science Foundation of China (Grant Nos. 12222506, 12347102, and 12174184). We are grateful to the High Performance Computing Center (HPCC) of Nanjing University for performing the numerical calculations in this paper on its blade cluster system.

Molecular dynamics simulations on the interactions between nucleic acids and a phospholipid bilayer

Yao Xu(徐耀)¹, Shu-Wei Huang(黄舒伟)¹, Hong-Ming Ding(丁泓铭)^2,†, and Yu-Qiang Ma(马余强)¹

1 National Laboratory of Solid State Microstructures and Department of Physics, Collaborative Innovation Center of Advanced Microstructures, Nanjing University, Nanjing 210093, China;
2 Center for Soft Condensed Matter Physics and Interdisciplinary Research, School of Physical Science and Technology, Soochow University, Suzhou 215006, China

Received:2023-10-02 Revised:2023-11-10 Accepted:2023-12-01 Online:2024-01-16 Published:2024-01-16
Contact: Hong-Ming Ding E-mail:dinghm@suda.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China (Grant Nos. 12222506, 12347102, and 12174184). We are grateful to the High Performance Computing Center (HPCC) of Nanjing University for performing the numerical calculations in this paper on its blade cluster system.

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摘要/Abstract

摘要： Recently, lipid nanoparticles (LNPs) have been extensively investigated as non-viral carriers of nucleic acid vaccines due to their high transport efficiency, safety, and straightforward production and scalability. However, the molecular mechanism underlying the interactions between nucleic acids and phospholipid bilayers within LNPs remains elusive. In this study, we employed the all-atom molecular dynamics simulation to investigate the interactions between single-stranded nucleic acids and a phospholipid bilayer. Our findings revealed that hydrophilic bases, specifically G in single-stranded RNA (ssRNA) and single-stranded DNA (ssDNA), displayed a higher propensity to form hydrogen bonds with phospholipid head groups. Notably, ssRNA exhibited stronger binding energy than ssDNA. Furthermore, divalent ions, particularly Ca²⁺, facilitated the binding of ssRNA to phospholipids due to their higher binding energy and lower dissociation rate from phospholipids. Overall, our study provides valuable insights into the molecular mechanisms underlying nucleic acid-phospholipid interactions, with potential implications for the nucleic acids in biotherapies, particularly in the context of lipid carriers.

关键词: RNA, DNA, lipid bilayer, molecular dynamics, interface interaction, divalent cation

Abstract: Recently, lipid nanoparticles (LNPs) have been extensively investigated as non-viral carriers of nucleic acid vaccines due to their high transport efficiency, safety, and straightforward production and scalability. However, the molecular mechanism underlying the interactions between nucleic acids and phospholipid bilayers within LNPs remains elusive. In this study, we employed the all-atom molecular dynamics simulation to investigate the interactions between single-stranded nucleic acids and a phospholipid bilayer. Our findings revealed that hydrophilic bases, specifically G in single-stranded RNA (ssRNA) and single-stranded DNA (ssDNA), displayed a higher propensity to form hydrogen bonds with phospholipid head groups. Notably, ssRNA exhibited stronger binding energy than ssDNA. Furthermore, divalent ions, particularly Ca²⁺, facilitated the binding of ssRNA to phospholipids due to their higher binding energy and lower dissociation rate from phospholipids. Overall, our study provides valuable insights into the molecular mechanisms underlying nucleic acid-phospholipid interactions, with potential implications for the nucleic acids in biotherapies, particularly in the context of lipid carriers.

Key words: RNA, DNA, lipid bilayer, molecular dynamics, interface interaction, divalent cation

中图分类号: (Lipids)

87.14.Cc

87.14.G- (Nucleic acids) 87.15.ap (Molecular dynamics simulation) 87.16.D- (Membranes, bilayers, and vesicles)

Yao Xu(徐耀), Shu-Wei Huang(黄舒伟), Hong-Ming Ding(丁泓铭), and Yu-Qiang Ma(马余强). Molecular dynamics simulations on the interactions between nucleic acids and a phospholipid bilayer[J]. 中国物理B, 2024, 33(2): 28701-028701.

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Molecular dynamics simulations on the interactions between nucleic acids and a phospholipid bilayer

Molecular dynamics simulations on the interactions between nucleic acids and a phospholipid bilayer

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