Department of Bioinformatics, School of Computer and Information Sciences, Galgotias University, Greater Noida, India,
Cell Biochem Biophys. 2013 Nov;67(2):645-56. doi: 10.1007/s12013-013-9553-4.
Serum C-reactive protein (CRP) is used as a marker of inflammation in several diseases including autoimmune disease and cardiovascular disease. CRP, a member of the pentraxin family, is comprised of five identical subunits. CRP has diverse ligand-binding properties which depend upon different structural states of CRP. However, little is known about the molecular dynamics and interaction properties of CRP. In this study, we used SAPS, SCRATCH protein predictor, PDBsum, ConSurf, ProtScale, Drawhca, ASAView, SCide and SRide server and performed comprehensive analyses of molecular dynamics, protein-protein and residue-residue interactions of CRP. We used 1GNH.pdb file for the crystal structure of human CRP which generated two pentamers (ABCDE and FGHIJ). The number of residues involved in residue-residue interactions between A-B, B-C, C-D, D-E, F-G, G-H, H-I, I-J, A-E and F-J subunits were 12, 11, 10, 11, 12, 11, 10, 11, 10 and 10, respectively. Fifteen antiparallel β sheets were involved in β-sheet topology, and five β hairpins were involved in forming the secondary structure. Analysis of hydrophobic segment distribution revealed deviations in surface hydrophobicity at different cavities present in CRP. Approximately 33 % of all residues were involved in the stabilization centers. We show that the bioinformatics tools can provide a rapid method to predict molecular dynamics and interaction properties of CRP. Our prediction of molecular dynamics and interaction properties of CRP combined with the modeling data based on the known 3D structure of CRP is helpful in designing stable forms of CRP mutants for structure-function studies of CRP and may facilitate in silico drug design for therapeutic targeting of CRP.
血清 C-反应蛋白（CRP）作为多种疾病（包括自身免疫性疾病和心血管疾病）炎症的标志物。CRP 是五聚素家族的一员，由五个相同的亚基组成。CRP 具有多种配体结合特性，这取决于 CRP 的不同结构状态。然而，CRP 的分子动力学和相互作用特性知之甚少。在这项研究中，我们使用了 SAPS、SCRATCH 蛋白预测器、PDBsum、ConSurf、ProtScale、Drawhca、ASAView、SCide 和 SRide 服务器，并对 CRP 的分子动力学、蛋白质-蛋白质和残基-残基相互作用进行了综合分析。我们使用 1GNH.pdb 文件作为人类 CRP 的晶体结构，生成了两个五聚体（ABCDE 和 FGHIJ）。A-B、B-C、C-D、D-E、F-G、G-H、H-I、I-J、A-E 和 F-J 亚基之间的残基-残基相互作用涉及的残基数分别为 12、11、10、11、12、11、10、11、10 和 10。15 个反平行 β 片层参与 β 片层拓扑结构，5 个 β 发夹参与形成二级结构。疏水性片段分布分析表明，CRP 中不同腔室的表面疏水性存在偏差。大约 33%的残基参与了稳定中心。我们表明，生物信息学工具可以提供一种快速预测 CRP 分子动力学和相互作用特性的方法。我们对 CRP 分子动力学和相互作用特性的预测，结合基于 CRP 已知 3D 结构的建模数据，有助于设计 CRP 突变体的稳定形式，进行 CRP 的结构功能研究，并为 CRP 的靶向治疗药物设计提供计算辅助。
