Abstract
The horizon of drug discovery is currently expanding to target and modulate protein-protein interactions (PPIs) in globular proteins and intrinsically disordered proteins that are involved in various diseases. To either interrupt or stabilize PPIs, the 3D structure of target protein-protein (or protein-peptide) complexes can be exploited to rationally design PPI modulators (inhibitors or stabilizers) through structure-based molecular design. In this review, we present an overview of experimental and computational methods that can be used to determine 3D structures of protein-protein complexes. Several approaches including rational and in silico methods that can be applied to design peptides, peptidomimetics and small compounds by utilization of determined 3D protein-protein/peptide complexes are summarized and illustrated.
Original language | English |
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Pages (from-to) | 1015-1033 |
Number of pages | 19 |
Journal | Future Medicinal Chemistry |
Volume | 11 |
Issue number | 9 |
DOIs | |
Publication status | Published - May 2019 |
Keywords
- intrinsically disordered proteins
- peptide design
- peptidomimetics
- PPI modulators
- protein-protein interactions
- MOLECULAR-DYNAMICS SIMULATIONS
- INTRINSICALLY DISORDERED PROTEINS
- SELECTIVE SMALL-MOLECULE
- PARTICLE CRYO-EM
- DRUG DISCOVERY
- IN-SILICO
- MASS-SPECTROMETRY
- BINDING-SITES
- WEB SERVER
- C-MYC