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. 2016 May 12;59(9):4087-102.
doi: 10.1021/acs.jmedchem.5b01875. Epub 2016 Feb 24.

A Real-World Perspective on Molecular Design

Affiliations

A Real-World Perspective on Molecular Design

Bernd Kuhn et al. J Med Chem. .

Abstract

We present a series of small molecule drug discovery case studies where computational methods were prospectively employed to impact Roche research projects, with the aim of highlighting those methods that provide real added value. Our brief accounts encompass a broad range of methods and techniques applied to a variety of enzymes and receptors. Most of these are based on judicious application of knowledge about molecular conformations and interactions: filling of lipophilic pockets to gain affinity or selectivity, addition of polar substituents, scaffold hopping, transfer of SAR, conformation analysis, and molecular overlays. A case study of sequence-driven focused screening is presented to illustrate how appropriate preprocessing of information enables effective exploitation of prior knowledge. We conclude that qualitative statements enabling chemists to focus on promising regions of chemical space are often more impactful than quantitative prediction.

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