Chou K C, Carlacci L
Computational Chemistry, Upjohn Research Laboratories, Kalamazoo, Michigan 49001.
Proteins. 1991;9(4):280-95. doi: 10.1002/prot.340090406.
The folding of a polypeptide into a parallel (alpha/beta)8 barrel (which is also called a circularly permuted beta 8 alpha 8 barrel) has been investigated in terms of energy minimization. According to the arrangement of hydrogen bonds between two neighboring beta-strands of the central barrel therein, such an alpha/beta barrel structure can be folded into six different types: (1) left-tilted, left-handed crossover; (2) left-tilted, right-handed crossover; (3) nontilted, left-handed crossover; (4) nontilted, right-handed crossover; (5) right-tilted, left-handed crossover; and (6) right-tilted, right-handed crossover. Here "tilt" refers to the orientational relation of the beta-strands to the axis of the central beta-barrel, and "crossover" to the beta alpha beta folding connection feature of the parallel beta-barrel. It has been found that the right-tilted, right-handed crossover alpha/beta barrel possesses much lower energy than the other five types of alpha/beta barrels, elucidating why the observed alpha/beta barrels in proteins always assume the form of right tilt and right-handed crossover connection. As observed, the beta-strands in the energy-minimized right-tilted, right-handed crossover (alpha/beta)8-barrel are of strong right-handed twist. The value of root-mean-square fits also indicates that the central barrel contained in the lowest energy (alpha/beta)8 structure thus found coincides very well with the observed 8-stranded parallel beta-barrel in triose phosphate isomerase (TIM). Furthermore, an energetic analysis has been made demonstrating why the right-tilt, right-handed crossover barrel is the most stable structure. Our calculations and analysis support the principle that it is possible to account for the main features of frequently occurring folding patterns in proteins by means of conformational energy calculations even for very complicated structures such as (alpha/beta)8 barrels.
已通过能量最小化研究了多肽折叠成平行（α/β）8桶状结构（也称为循环排列的β8α8桶状结构）的过程。根据中央桶状结构中相邻两条β链之间氢键的排列方式，这种α/β桶状结构可折叠成六种不同类型：（1）左倾斜、左手交叉；（2）左倾斜、右手交叉；（3）无倾斜、左手交叉；（4）无倾斜、右手交叉；（5）右倾斜、左手交叉；（6）右倾斜、右手交叉。这里的“倾斜”是指β链与中央β桶状结构轴的取向关系，“交叉”是指平行β桶状结构的βαβ折叠连接特征。已发现右倾斜、右手交叉的α/β桶状结构的能量比其他五种类型的α/β桶状结构低得多，这就解释了为什么在蛋白质中观察到的α/β桶状结构总是呈现右倾斜和右手交叉连接的形式。如观察到的那样，能量最小化的右倾斜、右手交叉（α/β）8桶状结构中的β链具有很强的右手扭曲。均方根拟合值还表明，由此发现的能量最低的（α/β）8结构中包含的中央桶状结构与磷酸丙糖异构酶（TIM）中观察到的8链平行β桶状结构非常吻合。此外，还进行了能量分析，以说明为什么右倾斜、右手交叉的桶状结构是最稳定的结构。我们的计算和分析支持这样一个原则，即即使对于非常复杂的结构，如（α/β）8桶状结构，也可以通过构象能量计算来解释蛋白质中频繁出现的折叠模式的主要特征。
