蛋白質屬於有機生物性高分子在生物系統中扮演各種重要的角色；而蛋白質的功能和其三維結構密切相關。蛋白質結構易受外在環境影響，如溶液酸鹼值、溫度、與濃度等。蛋白質目前可廣泛應用於不同領域，例如材料表面改質的添加劑、或是生物感測器探測分子等。因此，為瞭解蛋白質的結構和吸附界面的關係，本研究探討四種不同結構類型的蛋白質：α-螺旋、β-摺板、蛋白質可折疊為α-螺旋與β-摺板、和類澱粉蛋白短鍊，從水相吸附到氣液界面時結構的變化。利用分子動力學模擬，我們從微觀的角度分析蛋白質在水相和氣液界面的α-螺旋與β-摺板結構轉變時自由能變化。我們也提出蛋白質吸附的熱力學模型，用以估算蛋白質從水溶液吸附自氣液界面時所需要的自由能。我們也使用模擬來計算蛋白質的吸附能，藉以證實吸附模型的準確性。結果顯示，雖然從模擬和吸附模型得到的絕對吸附能有些差異，但是在吸附能的相對值上兩者的表現相當類似。因此我們認為此吸附模型可有效地推估α-螺旋與β-摺板結構的相對吸附自由能差，並對應到分子動力學模擬，結合為一完整的蛋白質吸附與構型轉換的熱力學迴圈。由此結合熱力學理論模型與分子模擬分析顯示，蛋白質於氣液界面時，其所排開的氣液接觸所造成氣液界面自由能之變化，是蛋白質吸附於界面的主要驅動力。而蛋白質的氨基酸序列，亦會影響其於氣液界面的二級結構傾向。進一步應用此一模型，我們也探討了類澱粉蛋白短鍊的纖維結構於氣液界面的吸附機制，由於疏水蛋白質支鍊基團的排列方式不同，我們發現纖維吸附面對於其吸附自由能有很大的影響。

Proteins are biological polymers that play many important roles in biological systems. The protein functions are highly correlated with the protein structures, which are affected by the solvent pH, temperature, and concentrations, etc. Protein have been applied in various fields, such as the substrate surface modifications, or the detecting molecules in the biosensors. In order to probe the effects of adsorbed interface on the protein structures, we investigate the protein conformational changes at the air/water interfaces for four different groups of proteins with different secondary structural characteristics, i.e. α-helix native, β-hairpin native, protein with equal α- and β-probability, and small amyloid peptide fibrils. We applied molecular dynamics combined with methadyanmics to calculate the protein conformational free energies in bulk water and at air/water interface. Furthermore, we developed a thermodynamics model for protein adsorption that focuses on two contributions, i.e. the desolvation of peptide residues and the reduction of air-water interfacial energy. Via the comparison between the peptide adsorption free energies at the air/water interface obtain by the theoretical prediction and simulation data, we found the proposed thermodynamic model accurately predicted the relative adsorption free energies of peptide in different conformations. Combining the protein adsorption free energies estimated from the thermodynamic model and the conformational free energy calculated from MD simulations, the complete thermodynamic cycle of protein adsorption and conformational change can be constructed. The results showed that the air/water interfacial energy changes, caused by the peptide allocation at the interface that inclines the air/water contact, are the main driving force of the protein adsorbing at the interface. Furthermore, the stability of protein secondary structure is also affected by the desolvation of the amino acid exposed to the air phase. Hence, the peptide sequence is important for the protein secondary structural preference at the interface. The model was further applied to investigate the adsorption free energy of small amyloid peptide fibrils. Our results showed that, owing to the arrangement of hydrophobic residues, the adsorbing fibril face play important roles for amyloid fibril adsorption at the air/water interface.

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