SPLINTS: small-molecule protein ligand interface stabilizers
نویسندگان
چکیده
منابع مشابه
Characterizing protein domain associations by Small-molecule ligand binding.
BACKGROUND Protein domains are evolutionarily conserved building blocks for protein structure and function, which are conventionally identified based on protein sequence or structure similarity. Small molecule binding domains are of great importance for the recognition of small molecules in biological systems and drug development. Many small molecules, including drugs, have been increasingly id...
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Artificial molecular switches that modulate protein activities in response to synthetic small molecules would serve as tools for exerting temporal and dose-dependent control over protein function. Self-splicing protein elements (inteins) are attractive starting points for the creation of such switches, because their insertion into a protein blocks the target protein's function until splicing oc...
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The destabilizing p53 cancer mutation Y220C creates an extended crevice on the surface of the protein that can be targeted by small-molecule stabilizers. Here, we identify different classes of small molecules that bind to this crevice and determine their binding modes by X-ray crystallography. These structures reveal two major conformational states of the pocket and a cryptic, transiently open ...
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OBJECTIVE The peroxisome proliferator-activated receptor-γ coactivator-1α1 (PGC-1α1) regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-1α1 activation is potentially beneficial for systemic metabolism. Pharmacological PGC-1α1 activators could be valuable tools in the fight against obesity and metabolic disease. Finding such compounds has been...
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Docking experiments of multiple compounds typically focus on a single protein. However, other targets provide information about relative binding efficiencies that is otherwise lacking. We developed a docking strategy that normalized results in both the ligand and target dimensions. This was applied to dock 287 approved small drugs with 35 peptide-binding proteins, including 15 true positives. T...
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ژورنال
عنوان ژورنال: Current Opinion in Structural Biology
سال: 2016
ISSN: 0959-440X
DOI: 10.1016/j.sbi.2016.01.004