Paper Citing NAMD - Abstract
Pietra, Francesco
From the Sequence to the Conformation of the Unabridged Transmembrane Domains TM1 and TM2 of the cASIC1a Ion Channel - A Parallel Tempering Approach
CHEMISTRY & BIODIVERSITY, 12:350-357, MAR 2015
This work was devised to unravel, along replica-exchange molecular-dynamics (REMD) simulations, the conformation in solution of the TM1 and TM2 transmembrane domains of the homotrimeric cASIC1a ion channel. This includes the head of TM1 and tail of TM2 that had previously defied X-ray diffraction analysis in the crystal. The structure of the open-channel complex of cASIC1a with psalmotoxin 1 (PcTx1) was chosen here as a basis, although, to make the simulations affordable, the procedure was limited to the missing portions, including a few adjacent -helical turns. The latter were held fixed during the simulations. Reassembling the whole subunit, by superimposition of the fixed portions, resulted in diving of both TM1 and TM2 as continuous -helices into the cytoplasm. At completion of this work, it appeared, from similar X-ray diffraction studies, that TM2 for both the complex of cASIC1a with the coral snake MitTx toxin, and the isolated desensitized ion channel, is discontinuous, with the triad G443-A444-S445 taking an extended, belt-like conformation. In this way, a filter ring against hydrated ions is formed by G443 in the trimer. Our REMD examination of this complex revealed a strong resistance by G443, and only that residue, to take dihedral-angle values compatible with an -helical conformation. This suggests that the flexibility of glycine alone does not explain formation of the extended, belt-like conformation of the triad G443-A444-S445. This also requires cooperation in the trimer.
