Reaching for high-hanging fruit in drug discovery at protein–protein interfaces

By J. Wells, Christopher L. McClendon. 2007

1,849 citations recorded by the source corpus.

Subfields: Cell Biology, Molecular Biology, Radiology, Nuclear Medicine and Imaging, Computational Chemistry & Drug Discovery

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Citations in the corpus

Molecular Docking and Structure-Based Drug Design Strategies (2015, background): “PPI inhibitors can be defined as small-molecule compounds that directly compete with one of the protein partners [116].”
Identification of direct residue contacts in protein–protein interaction by message passing (2009, neutral): “eij (new) (Ai , Aj ) = eij (old ) (Ai , Aj ) + Δ[ fij (Ai , Aj ) − Pij (Ai , Aj )] [3]”
Protein structure-based drug design: from docking to molecular dynamics. (2018, background): “The pioneering work of Wells and coworkers targeting the interleukin-8 established protein-protein interactions as challenging targets to comprise flat and featureless surfaces that are inherently flexible and adapt to different binders [50,51].”
Protein–protein interaction and quaternary structure (2008, background): “Thus, the unraveling of the underlying principles that govern protein– protein recognition is both central to the construction of the networks that define cell biology (Robinson et al. 2007) and instrumental in new drug development (Wells & McClendon, 2007).”
Molecular Shape and Medicinal Chemistry: A Perspective (2010, neutral): “91,92 Figure 19.”
The rise of fragment-based drug discovery. (2009, background): “The inhibition of a protein-protein interaction (PPI) of this type is a major challenge for medicinal chemistr”
High-resolution protein complexes from integrating genomic information with molecular simulation (2009, background): “In these systems, phosphoryl group flux between the input SK and the terminal RR is mediated via additional proteins, whose sole apparent purpose it is to hand the phosphoryl group from one to the next protein following a His-Asp-His-Asp cascade (1).”
Comprehensive Analysis of Loops at Protein-Protein Interfaces for Macrocycle Design (2014, neutral): “1 Some systematic methods have been developed to use structures of PPIs to identify druggable pockets and to design potential inhibitors.”
Systematic Analysis of Helical Protein Interfaces Reveals Targets for Synthetic Inhibitors (2010, methodology): “We propose that receptors with binding clefts are candidates for high-throughput screening efforts with small molecule libraries currently available to chemical biologists.(1,33) It is expected that several of these targets would not be of interest for inhibitor design owing to their biological func”