In silico-in vitro screening of protein-protein interactions: towards the next generation of therapeutics.
Protein-protein interactions (PPIs) have a pivotal role in many biological processes suggesting that targeting macromolecular complexes will open new avenues for the design of the next generation of therapeutics. A wide range of "in silico methods" can be used to facilitate the design of protein-protein modulators. Among these methods, virtual ligand screening, protein-protein docking, structural predictions and druggable pocket predictions have become established techniques for hit discovery and optimization. In this review, we first summarize some key data about protein-protein interfaces and introduce some recently reported computer methods pertaining to the field. URLs for several recent free packages or servers are also provided. Then, we discuss four studies aiming at developing PPI modulators through the combination of in silico and in vitro screening experiments.
Villoutreix
Bruno O
BO
c-Dithem, Inserm Consortium for Discovery and Innovation in Therapy and Medicine, France. bruno.villoutreix@univ-paris5.fr
Bastard
Karine
K
Sperandio
Olivier
O
Fahraeus
Robin
R
Poyet
Jean-Luc
JL
Calvo
Fabien
F
Déprez
Benoit
B
Miteva
Maria A
MA
D000465:Algorithms; D000595:Amino Acid Sequence; D001665:Binding Sites; D015195:Drug Design; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D020539:Sequence Analysis, Protein / Q000379:methods
D004364:Pharmaceutical Preparations; D011506:Proteins