Rational modulator design by exploitation of protein-protein complex structures

Wichapong, Kanin; Poelman, Hessel; Ercig, Bogac; Hrdinova, Johana; Liu, Xiaosong; Lutgens, Esther und Nicolaes, Gerry A. F. (2019): Rational modulator design by exploitation of protein-protein complex structures. In: Future Medicinal Chemistry, Bd. 11, Nr. 9: S. 1015-1033

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1756-8919
• Sprache: Englisch