Fooks H M, Martin A C R, Woolfson D N, Sessions R B, Hutchinson E G
School of Animal & Microbial Sciences, University of Reading, Whiteknights, P.O. Box 228, Reading RG6 6AJ, UK.
J Mol Biol. 2006 Feb 10;356(1):32-44. doi: 10.1016/j.jmb.2005.11.008. Epub 2005 Nov 22.
Statistical approaches have been applied to examine amino acid pairing preferences within parallel beta-sheets. The main chain hydrogen bonding pattern in parallel beta-sheets means that, for each residue pair, only one of the residues is involved in main chain hydrogen bonding with the strand containing the partner residue. We call this the hydrogen bonded (HB) residue and the partner residue the non-hydrogen bonded (nHB) residue, and differentiate between the favorability of a pair and that of its reverse pair, e.g. Asn(HB)-Thr(nHB)versus Thr(HB)-Asn(nHB). Significantly (p < or = 0.000001) favoured pairings were rationalised using stereochemical arguments. For instance, Asn(HB)-Thr(nHB) and Arg(HB)-Thr(nHB) were favoured pairs, where the residues adopted favoured chi1 rotamer positions that allowed side-chain interactions to occur. In contrast, Thr(HB)-Asn(nHB) and Thr(HB)-Arg(nHB) were not significantly favoured, and could only form side-chain interactions if the residues involved adopted less favourable chi1 conformations. The favourability of hydrophobic pairs e.g. Ile(HB)-Ile(nHB), Val(HB)-Val(nHB) and Leu(HB)-Ile(nHB) was explained by the residues adopting their most preferred chi1 and chi2 conformations, which enabled them to form nested arrangements. Cysteine-cysteine pairs are significantly favoured, although these do not form intrasheet disulphide bridges. Interactions between positively and negatively charged residues were asymmetrically preferred: those with the negatively charged residue at the HB position were more favoured. This trend was accounted for by the presence of general electrostatic interactions, which, based on analysis of distances between charged atoms, were likely to be stronger when the negatively charged residue is the HB partner. The Arg(HB)-Asp(nHB) interaction was an exception to this trend and its favorability was rationalised by the formation of specific side-chain interactions. This research provides rules that could be applied to protein structure prediction, comparative modelling and protein engineering and design. The methods used to analyse the pairing preferences are automated and detailed results are available (http://www.rubic.rdg.ac.uk/betapairprefsparallel/).
统计方法已被用于研究平行β折叠内的氨基酸配对偏好。平行β折叠中的主链氢键模式意味着，对于每一对残基，只有一个残基参与与含有配对残基的链的主链氢键形成。我们将此残基称为氢键结合（HB）残基，将配对残基称为非氢键结合（nHB）残基，并区分一对及其反向对的偏好性，例如天冬酰胺（HB）-苏氨酸（nHB）与苏氨酸（HB）-天冬酰胺（nHB）。使用立体化学论据对显著（p≤0.000001）偏好的配对进行了合理化解释。例如，天冬酰胺（HB）-苏氨酸（nHB）和精氨酸（HB）-苏氨酸（nHB）是偏好对，其中残基采用了允许侧链相互作用发生的偏好χ1旋转异构体位置。相比之下，苏氨酸（HB）-天冬酰胺（nHB）和苏氨酸（HB）-精氨酸（nHB）没有显著偏好，并且只有当所涉及的残基采用不太有利的χ1构象时才能形成侧链相互作用。疏水对的偏好性，例如异亮氨酸（HB）-异亮氨酸（nHB）、缬氨酸（HB）-缬氨酸（nHB）和亮氨酸（HB）-异亮氨酸（nHB），是由残基采用其最优选的χ1和χ2构象来解释的，这使它们能够形成嵌套排列。半胱氨酸-半胱氨酸对受到显著偏好，尽管它们不会形成片层内二硫键。带正电和带负电残基之间的相互作用不对称地受到偏好：那些带负电残基处于HB位置的相互作用更受青睐。这种趋势是由一般静电相互作用的存在所解释的，基于对带电原子之间距离的分析，当带负电残基是HB配对伙伴时，静电相互作用可能更强。精氨酸（HB）-天冬氨酸（nHB）相互作用是这种趋势的一个例外，其偏好性通过特定侧链相互作用的形成而合理化。这项研究提供了可应用于蛋白质结构预测、比较建模以及蛋白质工程和设计的规则。用于分析配对偏好的方法是自动化的，并且可获得详细结果（http://www.rubic.rdg.ac.uk/betapairprefsparallel/）。
