Sequence analysis and homology modeling of TRPV5 and TRPV6 channels

TRPV5 and TRPV6 channels are related to vigorous regulations under physiological, pathological, and therapeutic conditions. This study aims to predict the 3D structures of the TRPV channels by developing homology models based on the chosen multiple sequence alignment. In this study, we compared the results of the sequence alignments from three multiple sequence alignment programs; CLUSTALW, MAFFT and MUSCLE. The 3D structures of the TRPV channels were modeled based on the X-ray crystal structure of Kv1.2 channel (PDB code: 2R9R.pdb). Our results showed that the multiple sequence alignment of TRPV channels and the Kv1.2 channel generated by MAFFT showed the highest identical residues. Furthermore, based on structural assessment and evaluation, all the models showed the RMSD values of less than 2.7 Å, with Z-score closed to template structure and more than 99% of the residues located in allowed regions in Ramachandran plot. The IDAP residues form the pore region of the human TRPV5 model. While IDGP residues form the pore region of the mouse TRPV5 and TRPV6 as well as human TRPV6 channels.