publication . Article . 2012

Structural biology and drug discovery of difficult targets: the limits of ligandability.

Surade, Sachin; Blundell, Tom L.;
Open Access
  • Published: 01 Jan 2012 Journal: Chemistry & Biology, volume 19, pages 42-50 (issn: 1074-5521, Copyright policy)
  • Publisher: Elsevier BV
Abstract
Over the past decade, researchers in the pharmaceutical industry and academia have made retrospective analyses of successful drug campaigns in order to establish “rules” to guide the selection of new target proteins. They have identified features that are considered undesirable and some that make targets “unligandable.” This review focuses on the factors that make targets difficult: featureless binding sites, the lack of hydrogen-bond donors and acceptors, the presence of metal ions, the need for adaptive changes in conformation, and the lipophilicity of residues at the protein-ligand interface. Protein-protein interfaces of multiprotein assemblies share many of...
Subjects
free text keywords: Clinical Biochemistry, Molecular Medicine, Biochemistry, Molecular Biology, Pharmacology, Drug Discovery, General Medicine
Abstract
Over the past decade, researchers in the pharmaceutical industry and academia have made retrospective analyses of successful drug campaigns in order to establish “rules” to guide the selection of new target proteins. They have identified features that are considered undesirable and some that make targets “unligandable.” This review focuses on the factors that make targets difficult: featureless binding sites, the lack of hydrogen-bond donors and acceptors, the presence of metal ions, the need for adaptive changes in conformation, and the lipophilicity of residues at the protein-ligand interface. Protein-protein interfaces of multiprotein assemblies share many of...
Subjects
free text keywords: Clinical Biochemistry, Molecular Medicine, Biochemistry, Molecular Biology, Pharmacology, Drug Discovery, General Medicine
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