Wang Jin, Zhang Kun, Lu Hongyang, Wang Erkang
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, China.
Biophys J. 2006 Aug 1;91(3):866-72. doi: 10.1529/biophysj.105.074716. Epub 2006 Apr 14.
Biomolecular recognition often involves large conformational changes, sometimes even local unfolding. The identification of kinetic pathways has become a central issue in understanding the nature of binding. A new approach is proposed here to study the dynamics of this binding-folding process through the establishment of a path-integral framework on the underlying energy landscape. The dominant kinetic paths of binding and folding can be determined and quantified. The significant coupling between the binding and folding of biomolecules often exists in many important cellular processes. In this case, the corresponding kinetic paths of binding are shown to be intimately correlated with those of folding and the dynamics becomes quite cooperative. This implies that binding and folding happen concurrently. When the coupling between binding and folding is weak (strong), the kinetic process usually starts with significant folding (binding) first, with the binding (folding) later proceeding to the end. The kinetic rate can be obtained through the contributions from the dominant paths. The rate is shown to have a bell-shaped dependence on temperature in the concentration-saturated regime consistent with experiment. The changes of the kinetics that occur upon changing the parameters of the underlying binding-folding energy landscape are studied.
生物分子识别通常涉及大的构象变化，有时甚至是局部解折叠。确定动力学途径已成为理解结合本质的核心问题。本文提出一种新方法，通过在潜在能量景观上建立路径积分框架来研究这种结合-折叠过程的动力学。可以确定并量化结合和折叠的主导动力学途径。生物分子的结合与折叠之间的显著耦合在许多重要的细胞过程中经常存在。在这种情况下，相应的结合动力学途径显示出与折叠途径密切相关，并且动力学变得相当协同。这意味着结合和折叠同时发生。当结合与折叠之间的耦合较弱（较强）时，动力学过程通常首先从显著的折叠（结合）开始，随后结合（折叠）进行到底。动力学速率可以通过主导途径的贡献获得。在浓度饱和状态下，该速率显示出对温度呈钟形依赖，这与实验结果一致。研究了改变潜在结合-折叠能量景观参数时发生的动力学变化。
