中文摘要：

FKBP12（FK506-binding protein-12）是一种具有神经保护和促神经再生作用的蛋白．采用分子动力学模拟取样，运用MM—GBSA方法计算了FKBP12和3个抑制剂（GPI-1046，308和107）的绝对结合自由能，GPI-1046的结合能最小，308小于107的结合能．通过能量分解的方法考察了FKBP12蛋白的主要残基与抑制剂之间的相互作用和识别，计算结果表明：3个抑制剂具有相似的结合模式，I1e56和Tyr82主要表现为氢键作用，Tyr26，Phe46，Va155，I1e56，Trp59，Tyr82，Tyr87和Phe99形成疏水作用区．计算结果和实验结果吻合．

英文摘要：

FKBP 12 （FK506-binding protein-l 2） plays important roles in the treatment of nerve injuries and neurodegenerative disorders. In the paper, the absolute binding free energies of FKBP12 with three potent inhibitors （GPI-1046, 308 and 107） were calculated by molecular dynamics simulations with an MM-GBSA method, finding that GPI-i046 has the weakest binding energy, and 308 has weaker binding energy than 107. The analysis of detailed interaction energies provides insight into the protein-ligand binding mecha- nism. The results show that the three inhibitors bind to FKt3P 12 in very similar binding models, the inhibitors form hydrogen bonds with Ile56 and Tyr82, and the hydrophobic pocket is formed by Tyr26, Phe46, Va155, I1e56, Trp59, Tyr82, Tyr87 and Phe99. The calculated data agree well with the experimental ones.