应用死端排除法考虑分子对接中的侧链柔性

假设分子对接面的紧密堆积类似于蛋白质内部的紧密堆积，因此用于蛋白质内部的侧链构象预测方法，如死端排除法，可应用于分子对接面内的侧链构象预测。应用９个晶体结构对这一假设进行检验，结果表明假设基本正确。对２个蛋白酶与抑制剂的应用比较成功。９个配体中的７个有正确的均方根差的趋势。还发现受体结构的柔性较小，说明由于对接面的紧密堆积产生的侧链构象变化很小。根据这些结果，提出一个新的分子对接流程图，即在刚体对接后加入对接面中氨基酸残基的侧链构象预测。对一个蛋白酶与抑制剂的复合结构的应用表明对接中的正确解的信号与噪音比相对错误解增加了。

APPLICATION OF THE DEAD-END-ELIMINATIOD TO SOLVE THE SIDE CHAIN FLEXIBILITY PROBLEM IN MOLECULAR DOCKING

that the dose packing in the interface of molecular docking is similar to that in the interior of proteins. Therefore, mothods applied to the prediction of side chain conformation in proteins such as the dead-end-elimination method can also be applied to the prediction of side chain conformation in the inteface of molecular docking . This assumption has ho tested by using 9 crystal structures. The results show that the assumption is basically correct. Application 2 Crystal structures of proteases and their corresponding inhibitors was rather successful. Out of 9 ligand structures, 7 structures had the correct trend in root-mean -square deviation. The authors also discoved that flexibility of the receptor structures is rela tively samll. Hence, the conformational change owing to the close packing in the interface is very small. Based on these results, the authors propose a new proedure for molecular docking,namely, after rigid body docking the prediction of the side chain conformation of the amino acid residues is added inhibitor complex structure shows that the signal to noise ratio has increased for the correct solution in molecular docking, relative to the wrong solutions.