Salum Lívia B, Andricopulo Adriano D
Laboratório de Química Medicinal e Computacional, Centro de Biotecnologia Molecular Estrutural, Instituto de Física de São Carlos, Universidade de São Paulo, 13560-970 São Carlos, SP, Brazil.
Mol Divers. 2009 Aug;13(3):277-85. doi: 10.1007/s11030-009-9112-5. Epub 2009 Jan 31.
Drug design is a process driven by innovation and technological breakthroughs involving a combination of advanced experimental and computational methods. A broad variety of medicinal chemistry approaches can be used for the identification of hits, generation of leads, as well as to accelerate the optimization of leads into drug candidates. Quantitative structure-activity relationship (QSAR) methods are among the most important strategies that can be applied for the successful design of small molecule modulators having clinical utility. Hologram QSAR (HQSAR) is a modern 2D fragment-based QSAR method that employs specialized molecular fingerprints. HQSAR can be applied to large data sets of compounds, as well as traditional-size sets, being a versatile tool in drug design. The HQSAR approach has evolved from a classical use in the generation of standard QSAR models for data correlation and prediction into advanced drug design tools for virtual screening and pharmacokinetic property prediction. This paper provides a brief perspective on the evolution and current status of HQSAR, highlighting present challenges and new opportunities in drug design.
药物设计是一个由创新和技术突破驱动的过程，涉及先进的实验方法和计算方法的结合。各种各样的药物化学方法可用于确定活性分子、产生先导化合物，以及加速将先导化合物优化为候选药物。定量构效关系（QSAR）方法是可用于成功设计具有临床效用的小分子调节剂的最重要策略之一。全息定量构效关系（HQSAR）是一种基于二维片段的现代QSAR方法，它采用专门的分子指纹。HQSAR可应用于大量化合物数据集以及传统规模的数据集，是药物设计中的一种通用工具。HQSAR方法已从用于生成标准QSAR模型以进行数据关联和预测的经典用途，发展成为用于虚拟筛选和药代动力学性质预测的先进药物设计工具。本文简要介绍了HQSAR的发展历程和现状，重点介绍了药物设计中当前面临的挑战和新机遇。
