Abstract
We show that a water envelope network plays a critical role in protein-protein interactions (PPI). The potency of a PPI inhibitor is modulated by orders of magnitude on manipulation of the solvent envelope alone. The structure-activity relationship of PEX14 inhibitors was analyzed as an example using in silico and X-ray data.
MeSH terms
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Computer Simulation
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Crystallography, X-Ray
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Humans
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Membrane Proteins / chemistry
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Membrane Proteins / metabolism*
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Molecular Structure
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Peroxisome-Targeting Signal 1 Receptor / metabolism
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Proof of Concept Study
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Protein Binding / drug effects
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Protein Multimerization / drug effects*
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Protozoan Proteins / chemistry
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Protozoan Proteins / metabolism*
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Pyrazoles / chemistry*
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Pyrrolidines / chemistry*
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Structure-Activity Relationship
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Trypanosoma brucei brucei / chemistry
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Water / chemistry
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Water / metabolism*
Substances
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Membrane Proteins
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PEX14 protein, Trypanosoma brucei
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PEX5 protein, human
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Peroxisome-Targeting Signal 1 Receptor
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Protozoan Proteins
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Pyrazoles
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Pyrrolidines
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Water