中文摘要：

采用实验和理论化学研究相结合的方法研究分子间相互作用,这种在计算机上进行“模拟实验”与传统“有机化学实验”相辅相成的研究策略,正在成为有机化学研究的重要手段.本论文利用荧光光谱分析法来研究小分子有机化合物与蛋白底物之间的相互作用机制.利用先进的分子模拟软件,结合分子力学、量子力学和神经网络等方法与分子对接等理论化学手段,建立和优化相互作用的分子间形成复合物的空间构象,并且预测分子间相互作用的稳定性.用荧光光谱分析法对12种小分子有机化合物与DC-SIGN（DC-specific ICAM-3 grabbing nonintegrin）之间的相互作用进行了研究,结果与理论分子模型计算十分吻合.在这12种化合物中,1-脲基氨基甘露糖与DC-SIGN络合的效果最好.这一发现可能对研究新一代抗艾滋病药物有重要意义.

英文摘要：

Chemical experiments in combination with computational technologies have become a powerful tool for drug design and the study of macromolecular interactions. In this study, ligands or inhibitors of DC-specific ICAM-3 grabbing nonintegrin （DC-SIGN） were designed following molecular mechanical and quantum mechanical principles. The stability of oligonucleotide duplexes was predicted according to neutral network （NN） models. In addition, small synthetic molecules of monomannose derivatives and their interactions with DC-SIGN were investigated by fluorescence spectrum （FL） analysis. The results of 12 small molecules that interact with DC-SIGN were all fitted well into the computed theoretical molecular models. Among the 12 compounds analyzed, N-mannopyransosylsemicarbazide was determined to be the best ligand for DC-SIGN binding. Our discovery provided important evidence for novel drug design approaches, and might be particularly used for developing new classes of anti-HIV agents.