Sattelle Benedict M, Almond Andrew
Faculty of Life Sciences, Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
Phys Chem Chem Phys. 2014 May 7;16(17):8119-26. doi: 10.1039/c4cp00570h.
Amylose, a component of starch with increasing biotechnological significance, is a linear glucose polysaccharide that self-organizes into single- and double-helical assemblies. Starch granule packing, gelation and inclusion-complex formation result from finely balanced macromolecular kinetics that have eluded precise experimental quantification. Here, graphics processing unit (GPU) accelerated multi-microsecond aqueous simulations are employed to explore conformational kinetics in model single- and double-stranded amylose. The all-atom dynamics concur with prior X-ray and NMR data while surprising and previously overlooked microsecond helix-coil, glycosidic linkage and pyranose ring exchange are hypothesized. In a dodecasaccharide, single-helical collapse was correlated with linkages and rings transitioning from their expected syn and (4)C1 chair conformers. The associated microsecond exchange rates were dependent on proximity to the termini and chain length (comparing hexa- and trisaccharides), while kinetic features of dodecasaccharide linkage and ring flexing are proposed to be a good model for polymers. Similar length double-helices were stable on microsecond timescales but the parallel configuration was sturdier than the antiparallel equivalent. In both, tertiary organization restricted local chain dynamics, implying that simulations of single amylose strands cannot be extrapolated to dimers. Unbiased multi-microsecond simulations of amylose are proposed as a valuable route to probing macromolecular kinetics in water, assessing the impact of chemical modifications on helical stability and accelerating the development of new biotechnologies.
直链淀粉是淀粉的一种成分,其生物技术意义日益凸显,它是一种线性葡萄糖多糖,能自组装成单螺旋和双螺旋聚集体。淀粉颗粒堆积、凝胶化和包合物形成源于精细平衡的大分子动力学,而这种动力学一直难以进行精确的实验量化。在此,利用图形处理单元(GPU)加速的多微秒水相模拟来探究模型单链和双链直链淀粉的构象动力学。全原子动力学与先前的X射线和核磁共振数据一致,同时推测出了令人惊讶且此前被忽视的微秒级螺旋 - 线圈、糖苷键和吡喃糖环交换。在一个十二糖中,单螺旋塌陷与从预期的顺式和(4)C1椅式构象转变的键和环相关。相关的微秒级交换速率取决于与末端的接近程度和链长(比较六糖和三糖),同时提出十二糖键和环弯曲的动力学特征是聚合物的良好模型。类似长度的双螺旋在微秒时间尺度上是稳定的,但平行构型比反平行构型更稳定。在这两种情况下,三级结构限制了局部链动力学,这意味着单链直链淀粉的模拟不能外推到二聚体。提出对直链淀粉进行无偏多微秒模拟是探索水中大分子动力学、评估化学修饰对螺旋稳定性的影响以及加速新生物技术发展的一条有价值的途径。