Abstract

We study the CaM-peptide interactions for four CaM-related peptides with different calcium equivalents, using the hCaM-M124C-mBBr biosensor and Molecular Dynamics (MD). Due to the high sensitivity of the biosensor, we were able to calculate five K_ds based on the number of calcium equivalents for each peptide, showing a directly proportional relationship between the degree of calcium saturation and the increased affinity for the Calspermin, nNOS, and skMLSK peptides; while the CaV1.1 peptide has a degree of affinity independent of the number of calcium equivalent. On the other hand, the MD studies were designed based on the experimental results; I) visualizing the effect of the gradual elimination of calcium in Holo-CaM and II) analyzing the CaM-Peptide complexes with and without calcium. We observe that the gradual addition of calcium increases the flexibility of Holo-CaM. Concerning CaM-Peptide complexes, it presents differences in both the ΔG_T and the RMSD. These results demonstrate the importance of the use of biosensors and the power of MD to make inferences in systems such as CaM-peptide complexes.

摘要

我们使用h CaM-M124C- mBBr生物传感器和分子动力学 (MD)研究了四种具有不同钙当量的 CaM 相关肽的 CaM-肽相互作用。由于生物传感器的高灵敏度，我们能够计算出五个K _ds基于每个肽的钙当量数，显示钙饱和程度与对 Calspermin、nNOS 和 skMLSK 肽的亲和力增加之间呈正比关系；而 CaV1.1 肽具有与钙当量数无关的亲和度。另一方面，MD研究是根据实验结果设计的；I) 可视化 Holo-CaM 中钙逐渐消除的效果和 II) 分析有和没有钙的 CaM-肽复合物。我们观察到钙的逐渐添加增加了 Holo-CaM 的灵活性。关于 CaM-肽复合物，它在 ΔG _T和 RMSD。这些结果证明了使用生物传感器的重要性和 MD 在系统中进行推断的重要性，例如 CaM-肽复合物。