Implications of protein flexibility for drug discovery

By S. Teague. 2003

695 citations recorded by the source corpus.

Subfields: Molecular Biology, Pharmacology

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

In Pharmacology

Citations in the corpus

Virtual ligand screening: strategies, perspectives and limitations (2006, background): “44 Teague, S.J. (2003) Implications of protein flexibility for drug discovery.”
Dynamics of proteins in solution (2019, background): “Moreover, protein internal dynamics allowing structural flexibility can increase the affinity between a drug and its target and is therefore fundamental to understanding the ways in which drugs exert biological effects (Teague, 2003).”
Small-molecule inhibitors of protein–protein interactions: progressing towards the dream (2004, background): “Therefore there might be binding-site conformations that are well-suited to small-molecule binding yet are not visible in a single crystal structur”
Local Protein Structures (2007, neutral): “intrinsic flexibility of protein structure [268, 269].”
Structure-based maximal affinity model predicts small-molecule druggability (2007, methodology): “The current method is meant to address only the specified binding site and does not take into account the possibility of substantial flexibility or inhibition at allosteric pockets, both of which are important considerations in drug desig”
Bridging Molecular Docking to Molecular Dynamics in Exploring Ligand-Protein Recognition Process: An Overview (2018, background): “However, the binding of non-peptidomimetic ligands to renin has shown huge structural rearrangement of the protein (Teague, 2003), addressing the problem of considering protein ﬂexibility in drug design campaigns.”
Protein–ligand docking: Current status and future challenges (2006, background): “allow increased affinity to be achieved between a given drug and its target.(4) Furthermore, binding-site location”
Rational Approaches to Improving Selectivity in Drug Design (2012, background): “While it is possible that modifications introduced to clash with one conformation of a decoy can potentially be alleviated by reorganization of the decoy structure, 39 in many cases, as has been shown here, the binding pocket is rigid enough to avoid this problem.”
Molecular docking: a powerful approach for structure-based drug discovery. (2011, background): “According to the definition given by Teague [106], conformer selection refers to a process when a ligand selectively binds to a favorable conformation from a number of protein conformations; conformational induction describes a process in which the ligand converts the protein into a conformation tha”
Computer-aided drug-discovery techniques that account for receptor flexibility. (2010, neutral): “Crystal structures of bound protein–ligand complexes routinely demonstrate that 70–100% of the ligand is buried in the protein binding site, suggesting that binding-site residues ‘wrap around’ the ligand after the initial binding event [6].”