Department of Physical Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata-700032, India.
Phys Chem Chem Phys. 2017 May 10;19(18):11678-11689. doi: 10.1039/c7cp00221a.
The mechanism of ice recognition by antifreeze protein (AFP) is a topic of recent interest. Here, using equilibrium simulations and free energy calculations, we provide structural rationale to the observed experimental anomalies on type I AFP (wfAFP isoform HPLC6) and its mutants as well as probe the molecular origin of ice recognition by them. Our results clearly demonstrate that the interplay between the conformational and hydration properties dictates the ice binding ability of type I AFP and its mutants. We find that HPLC6 exists as a highly stable long helix which adsorbs on the ice surface through the ordered water cages around the CH group of threonine (THR) residues, rather than directly binding to the ice surface via threonine (THR) through hydrogen bonding. Upon mutating THR with serine (SER), the straight helix conformation of HPLC6 disappears and the most stable conformation is a kinked helix devoid of ice binding ability. Free energy calculations reveal that there is a dynamic equilibrium between straight and bent helical conformations in the case of a valine (VAL) mutant. The straight long helical form of the VAL mutant also has the ability to form an ordered water cage structure around the CH groups of the VAL residues and thereby efficiently adsorbs on an ice plane similar to the wild type AFP.
抗冻蛋白 (AFP) 识别冰的机制是最近备受关注的话题。在这里，我们使用平衡模拟和自由能计算，为观察到的 I 型 AFP（wfAFP 同工型 HPLC6）及其突变体的实验异常提供结构依据，并探讨它们识别冰的分子起源。我们的结果清楚地表明，构象和水合性质的相互作用决定了 I 型 AFP 及其突变体的冰结合能力。我们发现 HPLC6 作为一个高度稳定的长螺旋存在，通过围绕苏氨酸 (THR) 残基 CH 基团的有序水笼吸附在冰表面上，而不是通过氢键直接与冰表面上的 THR 结合。在 THR 突变为丝氨酸 (SER) 后，HPLC6 的直链螺旋构象消失，最稳定的构象是没有冰结合能力的扭曲螺旋。自由能计算表明，在 VAL 突变体的情况下，直链和弯曲螺旋构象之间存在动态平衡。VAL 突变体的直链长螺旋形式也能够在 VAL 残基的 CH 基团周围形成有序的水笼结构，从而有效地吸附在类似于野生型 AFP 的冰面上。
