蛋白質於固體表面的吸附現象在生醫工程應用上，例如醫療植入、生醫檢測晶片、藥物釋放系統以及組織工程，扮演相當重要的角色。在此研究中，我們利用了分子動力學模擬來研究蛇毒蛋白於混合不同長度的硫醇自組裝單分子膜上的吸附現象。藉由計算蛋白質與自組裝單分子膜的吸附能，我們可以得知其吸附強度。由模擬結果我們也探討了影響蛋白質吸附的物理機制。
除了靜態特性，我們也研究了蛋白質脫附的動態資訊，例如脫附力、蛋白質結構變化、作用能量以及平均力勢能。我們利用拉伸分子動力學模擬來研究蛋白質於自組裝單分子膜的脫附過程。在此研究中我們也將利用Jarzynski恆等式於非平衡態模擬下估計的平均力勢能與傳統的平衡態模擬的傘型取樣方法作比較，並探討模擬中所使用的拉伸速度以及取樣數目對利用Jarzynski恆等式估計平均力勢能的精準度的影響。
最後，我們研究蛇毒蛋白於混合不同長度的硫醇混合自組裝單分子膜上的吸附自由能。我們發現吸附自由能可藉由混合不同長度的硫醇所形成的混合自組裝單分子膜提升。利用成分分析，我們可以分別出在不同混合比例表面上，驅動其吸附的主因是由自組裝單分子膜表面或是水溶液分子而來。另外我們也進行了熱力學分項分析，如自由能、焓以及熵，此分析可幫助我們更為了解驅動蛋白質吸附的主要物理機制。

Understanding the protein adsorption onto solid surface is of critical importance in the field of bioengineering, such as medical implants, diagnostic biosensors, drug delivery systems, and tissue engineering. This study proposed molecular dynamics (MD) simulations to investigate the physical mechanism of cobra cardiotoxin (CTX) proteins adsorption on alkanethiol self-assembled monolayers (SAMs) composed of S(CH2)5CH3 and S(CH2)9CH3. The binding energy of the CTX protein to the SAM surface of different mixing ratios of alkanethiol chains was calculated. The physical mechanisms are examined to understand how these parameters affect the adsorption of a CTX protein on SAM surfaces.
Dynamic information, such as force, structural change, interaction energy, and potential of mean force (PMF), about the desorption of a single CTX protein from SAM surface was investigated by means of steered molecular dynamics (SMD) simulations. By applying Jarzynski’s equality, the PMF can be reconstructed from the SMD simulation. The PMFs, calculated by different estimators based upon Jarzynski’s equality, were compared with the conventional umbrella sampling method.
The free energies of a CTX protein adsorption onto SAMs with different mixing ratios were investigated. Enhancement of the adsorption affinity, i.e., the change in free energy of adsorption, for mixed SAMs was determined. A component analysis conducted to quantify the physical mechanisms that promoted CTX adsorption revealed contributions from both SAMs and the solvent. Further component analyses of thermodynamic properties, such as the free energy, enthalpy, and entropy, indicated that the contribution from SAMs was driven by enthalpy, and the contribution from the solvent was driven by entropy.

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