Membrane permeation processes and inter-molecular interactions of Cryptdin-4 studied by molecular dynamics simulations

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06037
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43020:Structural biochemistry-related
• Research Institution: Nagahama Institute of Bio-Science and Technology
• Principal Investigator: Takao Yoda 長浜バイオ大学, バイオサイエンス学部, 准教授 (50367900)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 抗菌ペプチド / 分子動力学シミュレーション

Outline of Final Research Achievements

Crytpdin-4 (Crp4) is an α-defensin expressed in the small intestine of mice. The interaction of Crp4 with negatively charged lipid bilayers increases the membrane permeability of small molecules. At the same time, Crp4 itself also permeates the membrane. Here, we performed membrane formation simulations to clarify the intermolecular interactions and to gain insight into the relationship between Crp4 membrane permeation and the increased membrane permeability of small molecules. Data analysis of our membrane self-assembly simulations in which Crp4 was found in the formed membranes revealed the spatial distribution of ions and small molecules such as water, head groups of lipids, and fluorescent dyes, as well as the characteristics of their intermolecular interactions.

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

抗菌ペプチドと脂質二重層の相互作用は、典型的な蛋白質間相互作用に見られる鍵と鍵穴のタイプの相互作用と比べると、立体構造的な特異性が低いと考えられる。この性質のため、分子動力学シミュレーションは有力な研究手段となる。本研究では、ペプチドの濃度や分子表面の性質、膜を構成する脂質の組成、水に溶けている低分子などの影響を受ける抗菌ペプチドの相互作用を膜形成シミュレーションにより研究した。得られた成果は活性メカニズムの理解に資すると期待される。