López-Vallejo Fabian, Caulfield Thomas, Martínez-Mayorga Karina, Giulianotti Marc A, Nefzi Adel, Houghten Richard A, Medina-Franco Jose L
Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA.
Comb Chem High Throughput Screen. 2011 Jul;14(6):475-87. doi: 10.2174/138620711795767866.
Virtual screening is increasingly being used in drug discovery programs with a growing number of successful applications. Experimental methodologies developed to speed up the drug discovery processes include high-throughput screening and combinatorial chemistry. The complementarities between computational and experimental screenings have been recognized and reviewed in the literature. Computational methods have also been used in the combinatorial chemistry field, in particular in library design. However, the integration of computational and combinatorial chemistry screenings has been attempted only recently. Combinatorial libraries (experimental or virtual) represent a notable source of chemically related compounds. Advances in combinatorial chemistry and deconvolution strategies, have enabled the rapid exploration of novel and dense regions in the chemical space. The present review is focused on the integration of virtual and experimental screening of combinatorial libraries. Applications of virtual screening to discover novel anticancer agents and our ongoing efforts towards the integration of virtual screening and combinatorial chemistry are also discussed.
虚拟筛选在药物研发项目中的应用日益广泛，成功案例不断增加。为加速药物研发进程而开发的实验方法包括高通量筛选和组合化学。计算筛选与实验筛选之间的互补性已在文献中得到认可和综述。计算方法也已应用于组合化学领域，尤其是在库设计方面。然而，计算筛选与组合化学筛选的整合直到最近才开始尝试。组合库（实验性或虚拟性）是化学相关化合物的重要来源。组合化学和去卷积策略的进展，使得能够快速探索化学空间中的新区域和密集区域。本综述聚焦于组合库的虚拟筛选与实验筛选的整合。还讨论了虚拟筛选在发现新型抗癌药物方面的应用，以及我们在虚拟筛选与组合化学整合方面正在进行的工作。
