DYNAMIC MODELS OF PROTEIN FOLDING

包括杰尼根和科维尔在内的一些调查人员在 美国国立卫生研究院、加州大学旧金山分校的迪尔小组和 哈佛大学的研究人员， 残基链的折叠。通常允许的集合 移动包括摆动（仅末端）、 两种可能状态之一的残基， 进行弯曲，曲轴在三维空间中移动。能量 矩阵是用来给能量之间的接触 链上不相邻的残基。大都会 算法用于搜索最低能量状态。当 最低能量状态被发现链已经折叠 成功地三次曲线的理想性质之一 这里描述的晶格模型是这样一个事实，即它不是 很难给出长度为27或更长的链的例子 可以用这种方式成功地折叠起来。 虽然立方晶格模型是一个有趣的模型， 研究折叠问题， 但是，这并不是一个非常现实的模型， proteins.为此，我们对 立方晶格模型，试图了解其 动力学，能量和熵之间的交换， 如果可能的话， 这些原则可能会导致更现实的 折页.有人建议，应该设法找到 使Tf/Tg最大化的模型参数（Bryngelson， 等）。或Tf/T（θ）（Camacho & Thirumalai）。的 我们发现这里提到的三个转变温度 只有TF才有帮助。Tg难以获得， 足够的精度是有用的，而T（θ）没有 到目前为止，它在预测中是有用的。我们有 开发了一种映射自由能表面的方法， 在Tf处展开分子。虽然这并不意味着 它确实提供了自由能表面的完整图像 这张图片对于调整参数非常有用 模型的。利用宫泽和杰尼根能源 我们已经能够调整矩阵的参数， 序列125个残基长，以便获得折叠， 合理的时间为大部分的审判。一 手稿正在准备中。

A number of investigators, including Jernigan and Covell at NIH, Dill's group at UCSF, and Shahknovich's group at Harvard, have studied cubic lattice models of the dynamic folding of a chain of residues. Usually the set of allowed moves consist of wiggles (ends only), planar flips of a residue between one of two possible states where the chain makes a bend, and crankshaft moves in 3-space. An energy matrix is used to give the energy of contact between residues not adjacent on the chain. The metropolis algorithm is used to search for a lowest energy state. When the lowest energy state is found the chain has folded successfully. One of the desirable properties of the cubic lattice model as here described is the fact that it is not difficult to give examples of chains of length 27 or more that can be successfully folded in this way. While the cubic lattice model has been an interesting model in which to examine the folding problem and has led to some insights, it is not a very realistic model for actual proteins. For this reason we have undertaken a study of the cubic lattice model in an attempt to understand its dynamics, the give and take between energy and entropy, with the purpose of uncovering if possible some general principles that might lead to more realistic models of folding. It has been proposed that one should try to find parameter's for the model which maximize Tf/Tg (Bryngelson, et al.) or Tf/T(theta) (Camacho & Thirumalai). Of the three transition temperatures mentioned here we have found only Tf to be helpful. Tg is difficult to obtain with sufficient accuracy to be useful and T(theta) has not proved to be useful in prediction thus far. We have developed a method of mapping the free energy surface by unfolding a molecule at Tf. While this does not give a complete picture of the free energy surface it does provide a picture that is very useful for adjusting the parameters of the model. By use of the Miyazawa & Jernigan energy matrix we have been able to adjust the parameters of a sequence 125 residues long so as to obtain folding in reasonable times for a large fraction of the trials. A manuscript is in preparation.