Bradbrook G M, Forshaw J R, Pérez S
CERMAV-CNRS, BP 53-38041 Grenoble, France.
Eur J Biochem. 2000 Jul;267(14):4545-55. doi: 10.1046/j.1432-1327.2000.01505.x.
Molecular dynamics (MD) simulations of Erythrina corallodendron lectin binding to a monosaccharide, alpha-galactose, and a disaccharide, N-acetyl lactosamine, have been performed in order to investigate the relationship between structure and thermodynamics. A simulated annealing protocol has been used to generate ensembles of structures for the two complexes, from which both qualitative and quantitative information on binding dynamics have been extracted. The ensembled averaged lectin-saccharide interaction enthalpy is equivalent for both sugars, whereas the calculation based on the X-ray structures does show a difference. Within large statistical errors, the calculated 'binding enthalpy' is also the same for the two systems. These errors arise largely from terms involving solvent and are a typical limitation of current MD simulations. Significant qualitative differences in binding between the two complexes are, however, observed over the ensembles. These could be important for unraveling the structure/thermodynamic relationship. Stated simply, there are a greater number of binding options available to the disaccharide compared to the monosaccharide. The implications of alternative binding states on thermodynamic parameters and the 'breaking of enthalpy-entropy compensation' are discussed. The role of solvent in lectin-saccharide complex formation is suggested to be significant.
为了研究结构与热力学之间的关系，对刺桐凝集素与单糖α-半乳糖和二糖N-乙酰乳糖胺的结合进行了分子动力学（MD）模拟。采用模拟退火协议生成了两种复合物的结构集合，从中提取了关于结合动力学的定性和定量信息。两种糖的集合平均凝集素-糖相互作用焓相等，而基于X射线结构的计算确实显示出差异。在较大的统计误差范围内，两个系统计算出的“结合焓”也相同。这些误差主要来自涉及溶剂的项，是当前MD模拟的典型局限性。然而，在整个集合中观察到两种复合物之间结合存在显著的定性差异。这些差异对于阐明结构/热力学关系可能很重要。简单地说，与单糖相比，二糖有更多的结合选择。讨论了替代结合状态对热力学参数的影响以及“焓-熵补偿的打破”。溶剂在凝集素-糖复合物形成中的作用被认为是显著的。
