Department of Applied Chemistry, Faculty of Engineering, University of Miyazaki, 1-1 Nishi, Gakuen Kibanadai, Miyazaki 889-2192, Japan.
J Phys Chem B. 2010 Jan 14;114(1):49-58. doi: 10.1021/jp908249r.
A computer docking study has been carried out on the crystal surfaces of cellulose Ialpha crystal models for the carbohydrate binding module (CBM) protein of the cellobiohydrolase Cel7A produced by Trichoderma reesei. Binding free energy maps between the CBM and the crystal surface were obtained by calculating the noncovalent interactions and the solvation free energy at grid points covering the area of the unit cell dimensions at the crystal surface. The potential maps obtained from grid searches of the hydrophobic (110) crystal surface exhibited two distinct potential wells. These reflected the 2-fold helical symmetry of the cellulose chain and had lower binding energies at the minimum positions than those for the hydrophilic (100) and (010) crystal surfaces. The CBM-cellulose crystal complex models derived from the minimum positions were then subjected to molecular dynamics (MD) simulation under an explicit solvent system. The (110) complex models exhibited larger affinities at the interface than the (100) and (010) ones. The CBM was more stably bound to the (110) surface when it was placed in an antiparallel orientation with respect to the cellulose fiber axis. In the solvated dynamics state, the curved (110) surface resulting from the fiber twist somewhat assisted a complementary fit with the CBM at the interface. In addition to the conventional Generalized Born (GB) method, the three-dimensional reference interaction site model (3D-RISM) theory was adopted to assess a solvent effect for the solvated MD trajectories. Large exothermic values for the noncovalent interactions appeared correlated to and were mostly compensated by endothermic values for the solvation free energy. These gave total binding free energies of -13 to -28 kcal/mol. Results also suggested that the hydrogen bonding scheme was not essential for substrate specificity.
已经对里氏木霉 Cel7A 纤维二糖水解酶的碳水化合物结合模块（CBM）蛋白的晶体表面模型进行了计算机对接研究。通过计算覆盖晶体表面单位晶胞尺寸区域的网格点上的非共价相互作用和溶剂化自由能，获得了 CBM 与晶体表面之间的结合自由能图谱。从网格搜索疏水（110）晶体表面获得的势能图显示了两个明显的势能阱。这反映了纤维素链的 2 重螺旋对称性，并且在最小位置处的结合能比亲水（100）和（010）晶体表面的结合能更低。然后，从最小位置导出的 CBM-纤维素晶体复合物模型在显式溶剂体系下进行分子动力学（MD）模拟。与（100）和（010）相比，（110）复合物模型在界面处表现出更大的亲和力。当 CBM 相对于纤维素纤维轴呈反平行取向时，它与（110）表面的结合更稳定。在溶剂化动力学状态下，纤维扭曲导致的弯曲（110）表面在界面处与 CBM 有些互补。除了常规的广义 Born（GB）方法外，还采用了三维参考相互作用位点模型（3D-RISM）理论来评估溶剂化 MD 轨迹的溶剂效应。非共价相互作用的较大放热值与溶剂化自由能的吸热值相关并在很大程度上得到补偿，从而产生了-13 至-28 kcal/mol 的总结合自由能。结果还表明，氢键方案对于底物特异性并非必不可少。
