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Designing the molecular future

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Abstract

Approximately 25 years ago the first computer applications were conceived for the purpose of automated ‘de novo’ drug design, prominent pioneering tools being ALADDIN, CAVEAT, GENOA, and DYLOMMS. Many of these early concepts were enabled by innovative techniques for ligand-receptor interaction modeling like GRID, MCSS, DOCK, and CoMFA, which still provide the theoretical framework for several more recently developed molecular design algorithms. After a first wave of software tools and groundbreaking applications in the 1990s—expressly GROW, GrowMol, LEGEND, and LUDI representing some of the key players—we are currently witnessing a renewed strong interest in this field. Innovative ideas for both receptor and ligand-based drug design have recently been published. We here provide a personal perspective on the evolution of de novo design, highlighting some of the historic achievements as well as possible future developments of this exciting field of research, which combines multiple scientific disciplines and is, like few other areas in chemistry, subject to continuous enthusiastic discussion and compassionate dispute.

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Acknowledgments

The author is grateful to Hugo Kubinyi for valuable feedback on the manuscript. This study was supported by the Swiss National Science Foundation (grant 205321-134783) and the OPO-Foundation Zurich.

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  1. Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH), Wolfgang-Pauli-Str. 10, 8093, Zurich, Switzerland

    Gisbert Schneider

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Schneider, G. Designing the molecular future. J Comput Aided Mol Des 26, 115–120 (2012). https://doi.org/10.1007/s10822-011-9485-2

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