THREONINE MUTATIONS IN PROLINE HELIX-II OF BACTERIORHODOPSIN - A MOLECULAR-DYNAMICS STUDY

Proline-containing helices are a part of many integral membrane protei ns. In addition, several such helices contain polar residues such as s erine and threonine in their helical segments. Such helices are known to play an important structural and functional role in membrane protei ns such as channels and receptors. Although it is known that proline i ntroduces a kink in the helix, the role of serine and threonine is not clear. In helices of globular proteins, these residues are often foun d to be involved in side chain to main chain hydrogen bonds. In the pr esent work, the role of these polar residues on the conformation and s tability of proline-containing helices was investigated using molecula r dynamics simulation studies. A native amino acid sequence of helix I I of the membrane protein bacteriorhodopsin was chosen for study. The 25-residue sequence has a proline residue at position 13, threonine re sidues at positions 9, 10 and 18 and a serine residue at position 22. Three sequences in the helical conformation were generated by mutation , all the Thr(3)/Ser(1), Thr/Ser on the N-terminal and C-terminal side of the proline by the non-polar residues of appropriate size. The fou r helical sequences thus obtained were subjected to molecular dynamics simulation for 500 ps and the results obtained were analysed for stru ctural features and to investigate the flexibility involved in these o ligopeptides. The results are interpreted in terms of the effect of th e Ser/Thr position with respect to proline.