Computational Approaches in Peptide and Protein Design: An Overview - Peptide and Protein Design for Biopharmaceutical Applications - page 41

without interfering with the extracellular loops connecting the helices or
with the N-terminal fragment. Since the extracellular loops are flexible, it is
quite possible that in the most 'open' conformation they will create an
opening wide enough for a cyclopentapeptide molecule to pass through
without significant sterical clashes between the cyclopentapeptide and the
loops. In fact, our computational modelling of binding of other peptides to
their corresponding GPCRs that accounted for the flexibility of the extra-
cellular loops (such as that of angiotensin II to the AT receptor type 2 [112])
confirmed this suggestion. However, one would need to perform similar
studies for the complex of FC131 and CXCR4 to be sure that this assump-
tion remains valid; such modelling could use the computational techniques
for restoring the large loops in GPCRs developed earlier [113].
ACKNOWLEDGEMENTS
The authors are grateful to Prof. Jay Ponder for sharing the unpublished
data regarding the AMOEBA polarizable force field and for general
discussion of the subject.
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