Computational Approaches in Peptide and Protein Design: An Overview - Peptide and Protein Design for Biopharmaceutical Applications - page 35

2.3.2 A 3D Model of the TM Region of CXCR4

Building a 3D model of the TM region of CXCR4 [7] was the next step in
modelling the complex. Generally, computational procedures used in this
step were the same as those developed and described previously [107,108].
CXCR4 belongs to the so-called rhodopsin-like group of GPCRs, so it was
logical to assume that the TM regions in the CXCR4 sequence could be found
by pairwise-sequence alignment of human CXCR4 with bovine rhodopsin.
The alignment was performed using the ClustalW program (http://
www.ch.embnet.org/software/ClustalW.html), as shown in Figure 2.5.
Assignment of the first and last residue in the TM helices of rhodopsin
wasgenerallybasedonthe(f, c) torsions ( 20 (f, c) 100)ofthe
X-ray structure (PDB entry 1F88 [10]; monomer A). Minor deviations from
these limitations were accepted for residues that were obviously part of a
helix, i.e. the Pro171-Leu172 fragment in the TM helix 4 (TMH4) of
rhodopsin. Proline was not assigned as a TM residue in rhodopsin when it
was located at the termini of the TM helices. Also, TMH1 was shortened by
two and one residues on the extra- and intracellular sides, respectively, and

Figure 2.5 Final alignment of the transmembrane regions of CXCR4 with the
rhodopsin sequence. Identical residues are shown with black background.

Numbering is based on the rhodopsin sequence