Cannon Daniel A, Ashkenasy Nurit, Tuttle Tell
WestCHEM, Department of Pure and Applied Chemistry, University of Strathclyde , 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.
Department of Materials Engineering and the Ilze Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev , Beer-Sheva, Israel.
J Phys Chem Lett. 2015 Oct 1;6(19):3944-9. doi: 10.1021/acs.jpclett.5b01733. Epub 2015 Sep 18.
Protein binding to surfaces is an important phenomenon in biology and in modern technological applications. Extensive experimental and theoretical research has been focused in recent years on revealing the factors that govern binding affinity to surfaces. Theoretical studies mainly focus on examining the contribution of the individual amino acids or, alternatively, the binding potential energies of the full peptide, which are unable to capture entropic contributions and neglect the dynamic nature of the system. We present here a methodology that involves the combination of nonequilibrium dynamics simulations with strategic mutation of polar residues to reveal the different factors governing the binding free energy of a peptide to a surface. Using a gold-binding peptide as an example, we show that relative binding free energies are a consequence of the balance between strong interactions of the peptide with the surface and the ability for the bulk solvent to stabilize the peptide.
蛋白质与表面的结合是生物学和现代技术应用中的一个重要现象。近年来，广泛的实验和理论研究集中于揭示控制与表面结合亲和力的因素。理论研究主要侧重于考察单个氨基酸的贡献，或者全肽的结合势能，而这些无法捕捉熵的贡献，并且忽略了系统的动态性质。我们在此提出一种方法，该方法涉及非平衡动力学模拟与极性残基的策略性突变相结合，以揭示控制肽与表面结合自由能的不同因素。以一种与金结合的肽为例，我们表明相对结合自由能是肽与表面之间强相互作用以及本体溶剂稳定肽的能力之间平衡的结果。
