人3型腺病毒六邻体蛋白同源建模及其进化轨迹分析

用同源建模方法构建了人3型腺病毒六邻体完整的空间结构, 对此结构模型的合理性进行检验, 并通过基于多重序列比对的进化轨迹分析发现, 不同型别的人腺病毒六邻体型特异性序列主要存在于六邻体的塔区上, 结合二级结构分析, 预测位于六邻体塔区表面的几个环区是型特异性中和表位的所在区域.

Homology Modeling and Evolution Trace Analysis of Human Adenovirus Type 3 Hexon

The human adenovirus(HAdV) can cause a broad spectrum of human infective diseases. The major coat protein of HAdV is hexon which processes a mass of neutralizing epitopes. The complete amino acid sequence of hexon was directly obtained by sequencing hexon PCR product of HAdV type 3 which was isolated in local hospital. Homology modeling was utilized to construct a three-dimensional(3D) hexon model, and it was subsequently refined by molecular mechanics(MM) and molecular dynamics(MD) simulations. The neutralizing epitopes were analyzed by evolutionary trace(ET) approach including multiple sequence alignment(MSA), sites conservatism calculation and 3D mapping of conservatism. It was found that the sites conservatism was lower closer to the tower region and the major variable sites of hexon were located in the tower region. These results indicated that the type-specific neutralizing epitopes of hexon lied in the surface loop regions of hexon tower.