Biomolecular Dynamics, Institute of Physics , Albert Ludwigs University , 79104 Freiburg , Germany.
J Chem Theory Comput. 2019 Oct 8;15(10):5750-5757. doi: 10.1021/acs.jctc.9b00598. Epub 2019 Sep 4.
To facilitate the observation of biomolecular energy transport in real time and with single-residue resolution, recent experiments by Baumann et al. ( 2019 , 58 , 2899 , DOI: 10.1002/anie.201812995 ) have used unnatural amino acids β-(1-azulenyl)alanine (Azu) and azidohomoalanine (Aha) to site-specifically inject and probe vibrational energy in proteins. To aid the interpretation of such experiments, non-equilibrium molecular dynamics simulations of the anisotropic energy flow in proteins TrpZip2 and PDZ3 domains are presented. On this account, an efficient simulation protocol is established that accurately mimics the excitation and probing steps of Azu and Aha. The simulations quantitatively reproduce the experimentally found cooling times of the solvated proteins at room temperature and predict that the cooling slows by a factor 2 below the glass temperature of water. In PDZ3, vibrational energy is shown to travel from the initially excited peptide ligand via a complex network of inter-residue contacts and backbone transport to distal regions of the protein. The supposed connection of these energy transport pathways with pathways of allosteric communication is discussed.
为了实时、单一位点分辨率地观察生物分子能量传递，Baumann 等人（2019 年，58，2899，DOI：10.1002/anie.201812995）最近的实验使用非天然氨基酸β-（1-薁基）丙氨酸（Azu）和叠氮高丙氨酸（Aha），在蛋白质中定点注入和探测振动能量。为了帮助解释这些实验，本文呈现了对 TrpZip2 和 PDZ3 结构域中各向异性能量流的非平衡分子动力学模拟。在此基础上，建立了一种高效的模拟方案，能够准确模拟 Azu 和 Aha 的激发和探测步骤。模拟结果定量再现了实验中在室温下溶剂化蛋白质的冷却时间，并预测冷却速度在水的玻璃化温度以下降低了 2 倍。在 PDZ3 中，振动能量从最初激发的肽配体通过复杂的残基间相互作用网络和骨架输运，传递到蛋白质的远端区域。讨论了这些能量传递途径与变构通讯途径的可能联系。
