Rayan A, Siew N, Cherno-Schwartz S, Matzner Y, Bautsch W, Goldblum A
The Department of Medicinal Chemistry, School of Pharmacy, Hebrew University of Jerusalem, Israel.
Recept Channels. 2000;7(2):121-37.
A novel algorithm was applied to the sequences of bacteriorhodopsin (BRh), of rhodopsin (Rh), and of the two human anaphylatoxin receptors, C5a-receptor (hC5aR) and C3a-receptor (hC3aR), that predicts their transmembrane domains (TMD) according to energy criteria alone, on the basis of their sequences and a template structure for each. Two consecutive criteria were applied for the predictions: the first is hydrophobicity of a sequence of residues, which determines the candidate stretches of residues that form one of the transmembrane helices. The second criterion is an energy function composed of inter residue contact energies, of hydrophobic contributions due to membrane exposure and of the interactions of a few residues with the phospholipid head groups. The sequence of candidate residues for each helix is longer than that of the template, and is finally determined by threading each of the candidate stretches on each of the template helices and evaluating the energy for all possible configurations. Contact energies between residues were taken from a database (Miyazawa S and Jernigan RL (1996) J Mol Biol 256 623-44). The algorithm predicts well the TMD structure of BRh based on its own template, and the TMD structure of Rh conforms well with the model of Baldwin et al (Baldwin JM Schertler GFX and Unger VM (1997) J Biol Chem 272 144-64). Results for the construction of the TMD of hC5aR and hC3aR were compared, employing the template structure of Rh. Most of the results for these receptors are in accord with alignments and with mutation experiments on hC5aR and hC3aR. The predictions may serve as a basis for future mutagenesis experiments of these receptors.
一种新算法被应用于细菌视紫红质（BRh）、视紫红质（Rh）以及两种人类过敏毒素受体——C5a受体（hC5aR）和C3a受体（hC3aR）的序列。该算法仅根据能量标准，基于它们各自的序列和模板结构来预测其跨膜结构域（TMD）。预测过程应用了两个连续的标准：第一个是残基序列的疏水性，它决定了形成跨膜螺旋之一的候选残基片段。第二个标准是一个能量函数，该函数由残基间接触能、膜暴露引起的疏水作用以及少数残基与磷脂头部基团的相互作用组成。每个螺旋的候选残基序列比模板的长，最终通过将每个候选片段与每个模板螺旋进行穿线比对，并评估所有可能构型的能量来确定。残基间的接触能取自一个数据库（Miyazawa S和Jernigan RL（1996年）《分子生物学杂志》256卷，623 - 44页）。该算法基于其自身模板能很好地预测BRh的TMD结构，并且Rh的TMD结构与Baldwin等人的模型（Baldwin JM、Schertler GFX和Unger VM（1997年）《生物化学杂志》272卷，144 - 64页）高度契合。利用Rh的模板结构，对hC5aR和hC3aR的TMD构建结果进行了比较。这些受体的大多数结果与比对以及对hC5aR和hC3aR进行的突变实验结果一致。这些预测可为这些受体未来的诱变实验提供基础。
