Kussell Edo, Shimada Jun, Shakhnovich Eugene I
Department of Biophysics, Harvard University, 240 Longwood Avenue, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5343-8. doi: 10.1073/pnas.072665799. Epub 2002 Apr 9.
A method for deriving all-atom protein folding potentials is presented and tested on a three-helix bundle protein, as well as on hairpin and helical sequences. The potentials obtained are composed of a contact term between pairs of atoms, and a local density term for each atom, mimicking solvent exposure preferences. Using this potential in an all-atom protein folding simulation, we repeatedly folded the three-helix bundle, with the lowest energy conformations having a C(alpha) distance rms from the native structure of less than 2 A. Similar results were obtained for the hairpin and helices by using different potentials. We derived potentials for several different proteins and found a high correlation between the derived parameters, suggesting that a potential of this form eventually could be found that folds multiple, unrelated proteins at the atomic level of detail.
本文提出了一种推导全原子蛋白质折叠势能的方法，并在一个三螺旋束蛋白以及发夹和螺旋序列上进行了测试。所获得的势能由原子对之间的接触项和每个原子的局部密度项组成，模拟了溶剂暴露偏好。在全原子蛋白质折叠模拟中使用这种势能，我们反复折叠三螺旋束，能量最低的构象与天然结构的Cα距离均方根小于2埃。通过使用不同的势能，发夹和螺旋也得到了类似的结果。我们推导了几种不同蛋白质的势能，发现推导参数之间具有高度相关性，这表明最终可能会找到一种这种形式的势能，能够在原子细节水平上折叠多种不相关的蛋白质。
