Department of Chemistry , University of Cambridge , Lenfield Road , Cambridge CB2 1EW , United Kingdom.
J Phys Chem B. 2018 Dec 20;122(50):11906-11921. doi: 10.1021/acs.jpcb.8b08371. Epub 2018 Dec 4.
Because of their inherent structural plasticity, intrinsically disordered proteins (IDPs) are generally difficult to characterize, both experimentally and via simulations. In this work, an approach for studying IDPs within the potential energy landscape framework is implemented and tested. Specifically, human CD4 receptor peptide, a disordered region implicated in HIV-1 infection, is characterized via basin-hopping parallel tempering and discrete path sampling. We also investigate the effects of three state-of-the-art AMBER force fields (ff99SB-ILDN, ff14ipq, and ff14SB) on the energy landscape. The results for ff99SB-ILDN exhibit the best agreement with experiment. Metastable states identified on the free energy surface help to unify, and are consistent with, several earlier predictions, and may serve as starting points for probing the reaction interface between CD4 and HIV-1 accessory proteins.
由于其固有的结构可塑性，无序蛋白质（IDPs）通常难以通过实验和模拟进行表征。在这项工作中，实现并测试了一种在势能景观框架内研究 IDPs 的方法。具体来说，研究了与 HIV-1 感染相关的无规则区域的人类 CD4 受体肽，通过 basin-hopping 并行温度控制和离散路径采样进行了特征描述。我们还研究了三种最先进的 AMBER 力场（ff99SB-ILDN、ff14ipq 和 ff14SB）对能量景观的影响。ff99SB-ILDN 的结果与实验结果吻合度最好。自由能表面上确定的亚稳态状态有助于统一并与之前的几个预测结果保持一致，并且可以作为探测 CD4 和 HIV-1 辅助蛋白之间反应界面的起点。
