Hazes B, Dijkstra B W
Laboratory of Chemical Physics, University of Groningen, The Netherlands.
Protein Eng. 1988 Jul;2(2):119-25. doi: 10.1093/protein/2.2.119.
As an aid in the selection of sites in a protein where a disulfide bond might be engineered, a computer program has been developed. The algorithm starts with the generation of C beta positions from the N, C alpha and C atom coordinates available from a three-dimensional model. A first set of residue pairs that might form a disulfide bond is selected on the basis of C beta-C beta distances between residues. Then, for each residue in this set, S gamma positions are generated, which satisfy the requirement that, with ideal values for the C alpha-C beta and C beta-S gamma bond lengths and for the bond angle at C beta, the distance between S gamma of residue 1 and C beta of residue 2 in a pair (determined by the bond angle at S gamma 2) is at, or very close to its ideal value. Usually two acceptable S gamma positions are found for each half cystine, resulting in up to four different conformations for the disulfide bond. Finally, these conformations are subjected to an energy minimization procedure to remove large deviations from ideal geometry and their final energies are calculated. User input determines which final conformations are energetically acceptable. These conformations are written to a file to allow further analysis and e.g. inspection on a computer graphics device.
为了辅助选择蛋白质中可能构建二硫键的位点，已开发了一个计算机程序。该算法首先根据三维模型中可得的N、Cα和C原子坐标生成Cβ位置。基于残基之间的Cβ - Cβ距离，选择可能形成二硫键的第一组残基对。然后，对于该组中的每个残基，生成Sγ位置，其需满足以下要求：对于Cα - Cβ和Cβ - Sγ键长以及Cβ处的键角取理想值时，一对残基中残基1的Sγ与残基2的Cβ之间的距离（由Sγ2处的键角确定）处于或非常接近其理想值。通常每个半胱氨酸会找到两个可接受的Sγ位置，从而导致二硫键最多有四种不同构象。最后，对这些构象进行能量最小化程序，以消除与理想几何形状的大偏差，并计算其最终能量。用户输入决定哪些最终构象在能量上是可接受的。这些构象被写入一个文件，以便进行进一步分析，例如在计算机图形设备上进行检查。
