Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, 950 Main Street, Worcester, Massachusetts 01610, USA.
J Chem Phys. 2013 Nov 14;139(18):185101. doi: 10.1063/1.4829768.
The thermodynamics and kinetics of protein folding and protein conformational changes are governed by the underlying free energy landscape. However, the multidimensional nature of the free energy landscape makes it difficult to describe. We propose to use a weighted-graph approach to depict the free energy landscape with the nodes on the graph representing the conformational states and the edge weights reflecting the free energy barriers between the states. Our graph is constructed from a molecular dynamics trajectory and does not involve projecting the multi-dimensional free energy landscape onto a low-dimensional space defined by a few order parameters. The calculation of free energy barriers was based on transition-path theory using the MSMBuilder2 package. We compare our graph with the widely used transition disconnectivity graph (TRDG) which is constructed from the same trajectory and show that our approach gives more accurate description of the free energy landscape than the TRDG approach even though the latter can be organized into a simple tree representation. The weighted-graph is a general approach and can be used on any complex system.
蛋白质折叠和构象变化的热力学和动力学由潜在的自由能景观决定。然而，自由能景观的多维性质使得其难以描述。我们建议使用加权图方法来描绘自由能景观，其中图上的节点代表构象状态，边的权重反映状态之间的自由能势垒。我们的图是从分子动力学轨迹构建的，不涉及将多维自由能景观投影到由几个序参数定义的低维空间上。自由能势垒的计算是基于使用 MSMBuilder2 包的转移路径理论进行的。我们将我们的图与广泛使用的过渡不连续性图（TRDG）进行了比较，该图是从同一轨迹构建的，并表明我们的方法比 TRDG 方法更能准确地描述自由能景观，尽管后者可以组织成简单的树状表示。加权图是一种通用方法，可以用于任何复杂系统。
