Understanding and predicting the specificity of small molecule protein interactions

生物体中的许多过程是通过小分子（“配体”）与蛋白质的相互作用来调节的。类似地，药剂的作用是刺激或抑制蛋白质。通过计算方法（“对接”）理解和预测这些相互作用是这个初级研究小组的目的。配体与多种蛋白质的结合既可以是高效的原因（在与多种疾病相关蛋白质相互作用的情况下），也可以是严重的副作用（在与不需要的蛋白质结合的情况下）。因此，调查的主要重点将放在相互作用的特异性上。该研究项目的目标是：(1)生成一个分子与多种激酶之间的对接预测相互作用的概况，并确定针对乳腺癌中暗示的激酶的药物；（II）通过对接小分子探针绘制激酶和g蛋白偶联受体的结合袋，并建议对现有配体进行化学修饰；（III）开发一种快速估计可旋转键构象熵的方法，以提高对配体结合亲和力的预测。

Many processes in living organisms are regulated through the interaction of small molecules (“ligands”) with proteins. Similarly, pharmaceutical agents are intended to stimulate or inhibit proteins. Understanding and predicting these interactions through computational methods (“docking”) is the purpose of this junior research group. The binding of a ligand to multiple proteins can either be the reason for high efficacy (in case of interaction with multiple diseaserelevant proteins) or severe side effects (in case of binding to undesired proteins). Thus, the main focus of the investigations will be on the specificity of the interactions. The goals of the research program are: (I) to generate a profile of the docking-predicted interactions between a molecule and multiple kinases and to identify agents against kinases implied in breast cancer; (II) to chart the binding pockets of kinases and G-protein-coupled receptors by docking small molecular probes and to suggest chemical modifications of existing ligands; and (III) to develop a fast method to estimate the conformational entropy of a rotatable bond in order to improve the prediction of ligand binding affinity.