重要文章：蛋白质怎么样折叠?Science(Oct.28,2011:Vol.334 No.6055)

Two reports in this issue probe single protein chains as they spontaneously unfold and refold. On page 517 of this issue, Lindorff-Larsen et al. (1) use state-of-the-art molecular dynamics (MD) simulations to elucidate the folding mechanisms of 12 different proteins. On page 512 of this issue, Stigler et al. (2) study the folding and unfolding of single calmodulin domains with single-molecule force spectroscopy. The results provide remarkable views of the folding process and address basic questions, such as whether proteins fold along pathways.

(1)p.512-516追踪钙调蛋白单分子的复杂折叠网络

The Complex Folding Network of Single Calmodulin Molecules

Johannes Stigler, Fabian Ziegler, Anja Gieseke, J. Christof M. Gebhardt, and Matthias Rief

ABSTRACT：Direct observation of the detailed conformational fluctuations of a single protein molecule en route to its folded state has so far been realized only in silico. We have used single-molecule force spectroscopy to study the folding transitions of single calmodulin molecules. High-resolution optical tweezers assays in combination with hidden Markov analysis reveal a complex network of on- and off-pathway intermediates. Cooperative and anticooperative interactions across domain boundaries can be observed directly. The folding network involves four intermediates. Two off-pathway intermediates exhibit non-native interdomain interactions and compete with the ultrafast productive folding pathway.

(2)p. 517-520快速折叠的蛋白质是怎么样折叠的？

How Fast-Folding Proteins Fold

Kresten Lindorff-Larsen1, Stefano Piana1, Ron O. Dror, David E. Shaw

ABSTRACT：An outstanding challenge in the field of molecular biology has been to understand the process by which proteins fold into their characteristic three-dimensional structures. Here, we report the results of atomic-level molecular dynamics simulations, over periods ranging between 100 μs and 1 ms, that reveal a set of common principles underlying the folding of 12 structurally diverse proteins. In simulations conducted with a single physics-based energy function, the proteins, representing all three major structural classes, spontaneously and repeatedly fold to their experimentally determined native structures. Early in the folding process, the protein backbone adopts a nativelike topology while certain secondary structure elements and a small number of nonlocal contacts form. In most cases, folding follows a single dominant route in which elements of the native structure appear in an order highly correlated with their propensity to form in the unfolded state.