Steinke Nicola, Genina Anna, Lorenz Christian D, McLain Sylvia E
Department of Biochemistry, University of Oxford , Oxford OX1 3QU, U.K.
Department of Physics, King's College London , London SE1 9NH, U.K.
J Phys Chem B. 2017 Mar 2;121(8):1866-1876. doi: 10.1021/acs.jpcb.6b12542. Epub 2017 Feb 14.
There is an ongoing debate as to how urea denatures proteins in solution. Using a combination of neutron scattering and computer simulation of a model peptide, KGPGK, it was found that the ionic strength and pH have a significant impact on the urea-peptide interaction. From the work presented here, it appears that urea first and foremost decreases the charge-based interactions in solution, such as the TFA-TFA association, before interacting with the peptide backbone via hydrogen bonds. This gives insight into the pH and salt concentration dependency of urea-caused protein denaturation and might unify direct and indirect theories of urea-induced protein denaturation. The observed differences between MD and neutron and X-ray diffraction data might show that MD, in this particular case, underestimates the influence of charged fluorinated solutes.
关于尿素如何使溶液中的蛋白质变性，目前仍存在争议。通过结合中子散射和对模型肽KGPGK进行计算机模拟，发现离子强度和pH值对尿素-肽相互作用有显著影响。从这里展示的工作来看，尿素似乎首先减少溶液中基于电荷的相互作用，比如三氟乙酸-三氟乙酸缔合，然后才通过氢键与肽主链相互作用。这为尿素导致蛋白质变性的pH值和盐浓度依赖性提供了见解，并且可能统一尿素诱导蛋白质变性的直接和间接理论。分子动力学（MD）与中子及X射线衍射数据之间观察到的差异可能表明，在这种特定情况下，分子动力学低估了带电氟化溶质的影响。
