Prieto Lidia, Rey Antonio
Departamento de Química Física I, Facultad de Ciencias Químicas, Universidad Complutense, E-28040 Madrid, Spain.
J Chem Phys. 2007 Apr 28;126(16):165103. doi: 10.1063/1.2727465.
The relative importance of local and long range interactions in the characteristics of the protein folding process has long been a matter of controversy. Computer simulations based on Gō-type models have been widely used to study this topic, but without much agreement on which type of interactions is more relevant for the foldability of a protein. In this work, the authors also employ a topology-based potential and simulation model to analyze the influence of local and long range interactions on the thermodynamics of the folding transition. The former are mainly used to control the degree of flexibility (or stiffness) of the chain, mostly appreciable in the unfolded (noncompact) state. Our results show the different effects that local and nonlocal interactions have on the entropy and the energy of the system. This implies that a balance between both types of interactions is required, so that a free energy barrier exists between the native and the denatured states. The variations in the contribution of both types of interactions have also a direct effect on the stability of the chain conformations, including the possible appearance of thermodynamic folding intermediates.
局部相互作用和长程相互作用在蛋白质折叠过程特性中的相对重要性长期以来一直存在争议。基于Gō型模型的计算机模拟已被广泛用于研究这一主题，但对于哪种类型的相互作用对蛋白质的可折叠性更相关，尚未达成太多共识。在这项工作中，作者还采用了基于拓扑的势和模拟模型来分析局部相互作用和长程相互作用对折叠转变热力学的影响。前者主要用于控制链的柔性（或刚性）程度，这在未折叠（非紧凑）状态下最为明显。我们的结果显示了局部相互作用和非局部相互作用对系统熵和能量的不同影响。这意味着需要两种相互作用之间达到平衡，以便在天然态和变性态之间存在自由能垒。两种相互作用贡献的变化也对链构象的稳定性有直接影响，包括热力学折叠中间体可能的出现。
