Division of Theoretical Chemistry, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden.
LINXS-Lund Institute of Advanced Neutron and X-ray Science, Scheelevägen 19, SE-223 70 Lund, Sweden.
J Chem Theory Comput. 2020 Mar 10;16(3):1924-1935. doi: 10.1021/acs.jctc.9b01190. Epub 2020 Feb 25.
Phosphorylation is one of the most abundant types of post-translational modifications of intrinsically disordered proteins (IDPs). This study examines the conformational changes in the 15-residue-long N-terminal fragment of the IDP statherin upon phosphorylation, using computer simulations with two different force fields: AMBER ff99SB-ILDN and CHARMM36m. The results from the simulations are compared with experimental small-angle X-ray scattering (SAXS) and circular dichroism data. In the unphosphorylated state, the two force fields are in excellent agreement regarding global structural properties such as size and shape. However, they exhibit some differences in the extent and type of the secondary structure. In the phosphorylated state, neither of the force fields performs well compared to the experimental data. Both force fields show a compaction of the peptide upon phosphorylation, greater than what is seen in SAXS experiments, although they differ in the local structure. While the CHARMM force field increases the fraction of bends in the peptide as a response to strong interactions between the phosphorylated residues and arginines, the AMBER force field shows an increase of the helical content in the N-terminal part of the peptide, where the phosphorylated residues reside, in better agreement with circular dichroism results.
磷酸化是无规卷曲蛋白质（IDP）中最丰富的翻译后修饰类型之一。本研究使用两种不同力场（AMBER ff99SB-ILDN 和 CHARMM36m）的计算机模拟，研究 IDP 牙本质基质蛋白的 15 个残基 N 端片段在磷酸化后的构象变化。模拟结果与实验小角 X 射线散射（SAXS）和圆二色性数据进行比较。在未磷酸化状态下，两种力场在大小和形状等整体结构特性方面非常吻合。然而，它们在二级结构的程度和类型上存在一些差异。在磷酸化状态下，与实验数据相比，两种力场的表现都不佳。两种力场都显示出肽的紧缩，比 SAXS 实验中观察到的更明显，尽管它们在局部结构上存在差异。虽然 CHARMM 力场由于磷酸化残基与精氨酸之间的强烈相互作用，增加了肽中的弯曲部分的分数，但 AMBER 力场显示出肽的 N 端部分（磷酸化残基所在的区域）的螺旋含量增加，与圆二色性结果更吻合。
