Hua Lan, Zhou Ruhong, Thirumalai D, Berne B J
Department of Chemistry, Columbia University, New York, NY 10027, USA.
Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16928-33. doi: 10.1073/pnas.0808427105. Epub 2008 Oct 28.
The mechanism of denaturation of proteins by urea is explored by using all-atom microseconds molecular dynamics simulations of hen lysozyme generated on BlueGene/L. Accumulation of urea around lysozyme shows that water molecules are expelled from the first hydration shell of the protein. We observe a 2-stage penetration of the protein, with urea penetrating the hydrophobic core before water, forming a "dry globule." The direct dispersion interaction between urea and the protein backbone and side chains is stronger than for water, which gives rise to the intrusion of urea into the protein interior and to urea's preferential binding to all regions of the protein. This is augmented by preferential hydrogen bond formation between the urea carbonyl and the backbone amides that contributes to the breaking of intrabackbone hydrogen bonds. Our study supports the "direct interaction mechanism" whereby urea has a stronger dispersion interaction with protein than water.
通过在BlueGene/L上生成的鸡溶菌酶全原子微秒分子动力学模拟，探索了尿素使蛋白质变性的机制。溶菌酶周围尿素的积累表明，水分子从蛋白质的第一水化层被排出。我们观察到尿素对蛋白质的渗透分为两个阶段，尿素在水之前穿透疏水核心，形成一个“干球”。尿素与蛋白质主链和侧链之间的直接色散相互作用比水更强，这导致尿素侵入蛋白质内部，并使尿素优先结合到蛋白质的所有区域。尿素羰基与主链酰胺之间优先形成氢键，这有助于主链内氢键的断裂，从而增强了上述作用。我们的研究支持“直接相互作用机制”，即尿素与蛋白质的色散相互作用比水更强。
