以粗粒徑分子動力學探討尾管彎矩剛性對噬菌體吸附行為之影響

Abstract

本研究針對噬菌體感染初期的吸附階段，探討尾管彎矩剛性與宿主細胞表面曲率對其吸附行為與效率之影響，並嘗試補足實驗觀察於時間與空間解析度上的限制。研究以 Douge 噬菌體為藍本，建構具物理參考性的二維粗粒徑模型，並採用粗粒徑分子動力學模擬方法，設計多組模擬情境進行系統性比較分析。模擬內容包含單一噬菌體於細胞表面附近之吸附行為、柔性與剛硬尾管條件下的結構變化，以及多顆噬菌體於平坦與具曲率細胞表面中的擴散與群體吸附特性。所有模擬皆採用 NVT 系綜並引入熱擾動條件，以捕捉吸附前後的構型演化與動態特徵。 模擬結果顯示，柔韌性尾管相較於剛硬尾管可更有效率地完成吸附，不僅吸附成功率較高，且所需時間較短、所需旋轉與橫向位移較小，展現出較佳的動態適應性。此外，在柔韌性尾管的多組模擬中均可觀察到一特有吸附機制：噬菌體先以衣殼接近細胞表面，底板完成附著後再由尾管驅動整體結構站立，最終完成穩定吸附。 另一方面，細胞表面幾何形貌亦對吸附效率產生明顯影響，具曲率的表面能有效提升短距離吸附事件之完成速率，整體平均吸附時間低於平坦表面條件，顯示曲率對於完成吸附行為具有積極作用。 本研究所建構之模擬系統與分析結果，除可作為實驗觀察的輔助與延伸，亦為噬菌體結構設計、表面功能化與未來精準醫療應用提供理論依據與模擬參考基礎。

This study explores the adsorption behavior of bacteriophages during the early infection phase, focusing on the effects of tail tube bending stiffness and host cell surface curvature. A physically grounded two-dimensional coarse-grained model of the Douge phage was developed, and molecular dynamics simulations were conducted under various mechanical and geometric conditions. Simulation scenarios included single-phage adsorption, comparisons of flexible versus rigid tail tubes, and multi-phage interactions with flat and curved surfaces. Results show that flexible tail tubes lead to higher adsorption success rates and faster attachment, requiring less rotation and displacement. A distinct multi-stage mechanism was observed: phages initially approach with the capsid, then attach via the baseplate, and finally stand upright driven by tail tube mechanics. Curved surfaces further improve adsorption efficiency by reducing completion time for short-range interactions. The findings provide theoretical insights into phage adsorption dynamics and offer guidance for future phage design and biomedical applications.