人血清白蛋白HSA (Human serum albumin) 具有可結合雙原子配位基 (如：O2，CO和NO) 的能力，因此在生物循環過程中扮演重要角色。在三種配位基中，氧氣的含量最豐富，而且與自由的血紅素 (Heme) 具最低的結合親和力。雙原子配位基O2的親和力是決定血紅素蛋白質功能的重要關鍵。在本研究中，使用全原子分子動態模擬去探討人血清白蛋白HSA的結構與動態上的性質，其中沒有O2的突變體為 HF和HL ，具O2的突變體為 HF-O2和HL-O2。模擬結果顯示，最初的wild-type HSA，其Tyr161結合鐵原子降低了與O2的結合能力，這與實驗觀察相同。血紅素基經由形成穩定的鹽橋結合蛋白質，而氫鍵的貢獻可被忽略。在雙重突變體中，突變不會改變主要的蛋白質二級結構（α-螺旋）。我們也發現了His與鐵結合可協助氧氣的結合。最後觀測了蛋白質域 (domain) 之間的運動。 The human serum albumin (HSA) plays an important role in many biological processes, which are affected by its ability to bind diatomic ligands, e.g. O2, CO, and NO. Out of three ligands, O2 is the most abundant and has the lowest binding affinity for free heme. Diatomic ligands affinity of O2 is one of the key issues for determining a heme protein function. In this study, all-atom molecular dynamics (MD) was employed to study the structural and dynamical properties of HSA, its mutants without O2 (HF and HL), and its mutants with O2 (HF-O2 and HL-O2). Simulations show that for the wild type HSA, the Tyr161 binds to the Fe atom implying for its low O2 binding ability, which is consistent with experimental observation. The heme group is bound with protein through the formation of stable salt bridges, while the contribution from hydrogen bonding can be ignored. For the double mutants, the mutations do not change the major secondary structure (α-helix) of protein. We also found that the His is bound with Fe in assisting the O2 binding. Finally, we observed the inter-domain motions.
