在基于化合物相似性的虚拟筛选实验中发现新型生物活性支架的能力已被研究,基于排名,投票,和共识评分协议。七个众所周知的药物靶标(CDK2,COX2,雌激素受体,神经氨酸酶,HIV-1蛋白酶,p38MAP激酶,凝血酶)已经组装,使得每个配体代表其独特的化学类型,从而确保配体之间的每个相似性识别事件构成支架跳跃事件。在一系列涉及9969种MDDR化合物作为阴性对照的虚拟筛选研究中,发现原子对描述符和3D药效基团指纹图谱结合排序,投票,共识评分策略在寻找新型生物活性支架方面表现良好。此外,与基于结构的方法相比,基于相似性的虚拟筛选通常具有更高的性能。该发现表明,关于从已知生物活性配体获得的靶标的信息与靶标结构的知识一样有价值,用于通过虚拟筛选鉴定新型生物活性支架。
The ability to find novel bioactive scaffolds in compound similarity-based virtual screening experiments has been studied comparing Tanimoto-based, ranking-based, voting, and
consensus scoring protocols. Ligand sets for seven well-known drug targets (CDK2, COX2, estrogen receptor, neuraminidase, HIV-1 protease, p38 MAP kinase, thrombin) have been assembled such that each ligand represents its own unique chemotype, thus ensuring that each similarity recognition event between ligands constitutes a scaffold hopping event. In a series of virtual screening studies involving 9969 MDDR compounds as negative controls it has been found that atom pair descriptors and 3D pharmacophore fingerprints combined with ranking, voting, and
consensus scoring strategies perform well in finding novel bioactive scaffolds. In addition, often superior performance has been observed for similarity-based virtual screening compared to structure-based methods. This finding suggests that information about a target obtained from known bioactive ligands is as valuable as knowledge of the target structures for identifying novel bioactive scaffolds through virtual screening.