快速折叠模型蛋白的类进化选择

Gutin A M, Abkevich V I, Shakhnovich E I

Harvard University, Department of Chemistry, Cambridge, MA 02138.

Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1282-6. doi: 10.1073/pnas.92.5.1282.

We propose an algorithm providing sequences of model proteins with rapid folding into a given target (native) conformation. This algorithm is applied to a chain of 27 residues on a cubic lattice. It generates sequences with folding 2 orders of magnitude faster than that of the practically random starting sequence. Thermodynamic analysis shows that the increase in speed is matched by an increase in stability: the evolved sequences are much more stable in their native conformation than the initial random sequence. The unfolding temperature for evolved sequences is slightly higher than the simulation temperature, bearing direct correspondence to the relatively low stability of real proteins.

我们提出了一种算法，该算法能生成可快速折叠成给定目标（天然）构象的模型蛋白质序列。此算法应用于立方晶格上由27个残基组成的链。它生成的序列折叠速度比实际随机起始序列快2个数量级。热力学分析表明，速度的提高伴随着稳定性的增加：进化后的序列在其天然构象中比初始随机序列稳定得多。进化后序列的解折叠温度略高于模拟温度，这与真实蛋白质相对较低的稳定性直接相关。