MOLECULAR-DYNAMICS SIMULATION OF PROTEIN DENATURATION - SOLVATION OF THE HYDROPHOBIC CORES AND SECONDARY STRUCTURE OF BARNASE
MOLECULAR-DYNAMICS SIMULATION OF PROTEIN DENATURATION - SOLVATION OF THE HYDROPHOBIC CORES AND SECONDARY STRUCTURE OF BARNASE
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DOI：
10.1073/pnas.91.5.1746
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发表时间：
1994-03-01
影响因子：
11.1
通讯作者：
KARPLUS, M
中科院分区：
文献类型：
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作者：
CAFLISCH, A;KARPLUS, M
采用高温分子动力学模拟方法研究了芽孢杆菌RNA酶从天然状态到致密小球的转变过程。观察到α-螺旋和β-折叠外链的部分破坏，水分子取代二级结构元件的氢键。同时，主要的α-螺旋远离β-折叠，暴露出主要的疏水核心，其许多非极性侧链，从表面附近的侧链开始，被氢键合的水分子溶剂化。该步骤涉及溶剂暴露表面积的显著增加;由于疏水效应导致的稳定性损失可能是解折叠反应中活化屏障的主要来源。这里描述的芽孢杆菌RNA酶变性的第一阶段的详细机制，包括水分子的基本作用，很可能是一般的蛋白质变性的代表。
The transition in barnase from the native state to a compact globule has been studied with high-temperature molecular dynamics simulations. A partial destruction of the alpha-helices and the outer strands of the beta-sheet is observed with water molecules replacing the hydrogen bonds of the secondary structural elements. Simultaneously, the main alpha-helix moves away from the beta-sheet and exposes the principal hydrophobic core, many of whose nonpolar side chains, beginning with the ones near the surface, become solvated by hydrogen-bonded water molecules. This step involves a significant increase in the solvent-exposed surface area; the resulting loss of stability due to the hydrophobic effect may be the major source of the activation barrier in the unfolding reaction. The detailed mechanism described here for the first stage of the denaturation of barnase, including the essential role of water molecules, is likely to be representative of protein denaturation, in general.