it is very hard to obtain experimentally solved structures of GPCR
multimers. Currently, the GPCR-OKB database holds information
of about 192 distinct GPCR multimers [75]. Among them only a
very small fraction has an available experimentally solved crystal
structure. Moreover, all of the available structures are homodimers,
whereas detailed structural insights into heteromers are completely
missing.
Numerous experimentally solved structures of individual pro-
teins forming the multimer (protomers) exist. Furthermore,
homology modeling is highly efficient in predicting their structure
[76], and thus it is tempting to utilize PPD for obtaining structural
insights into the structure of GPCR oligomers.
PPD is not commonly used to model complexes of transmem-
brane proteins (Fig.1). The same research group [78] published an
extension to the outer membrane phospholipase A protein
(OMPLA) of the docking-based protocols previously developed
for quaternary structure predictions of transmembrane oligomeric
proteins and for estimating mutational effects on the thermody-
namics of protein–protein and protein–DNA association.Fig. 2A schematic representation of two drug design strategies when targeting GPCR dimers: (a) Ligands that
stabilize and facilitate the formation of dimers; (b) ligands that prevent the formation of dimers, by competi-
tively binding to sites involved in GPCR-GPCR binding
Protein-Protein Docking 295