THE STABILITY OF TRANSMEMBRANE HELICES - A MOLECULAR-DYNAMICS STUDY ON THE ISOLATED HELICES OF BACTERIORHODOPSIN

Bacteriorhodopsin (bR) continues to be a proven testing ground for the study of integral membrane proteins (IMPs). It is important to study the stability of the individual helices of bR, as they are postulated to exist as independently stable transmembmne helices (TMHs) and also for their utility as templates for modeling other IMPs with the postul ated seven-helix bundle topology. Toward this purpose, the seven helic es of bR have been studied by molecular dynamics simulation in this st udy. The suitability of using the backbone-dependent rotamer library o f side-chain conformations arrived at from the data base of globular p rotein structures in the case TMHs has been tested by another set of ? helix simulations with the side-chain orientations taken from this li brary. The influence of the residue's net charge oil the helix stabili ty was examined by simulating the helices III, IV, and VI (from both o f the above sets of helices) with zero net charge on the side chains. The results of these 20 simulations demonstrate in general the stabili ty of the isolated helices of bR in conformity with the two-stage hypo thesis of IMP folding. However, the helices I, II, V, and VII are more stable than the other three helices. The helical nature of certain re gions of III, IV, and VI are influenced by factors such as the net cha rge and orientation of several residues. It is seen that the residues Arg, Lys, Asp, and Glu (charged residues), and Ser, Thr, Gly, and Pro, play a crucial role in the stability of the helices of bR. The backbo ne-dependent rotamer library for the side chains is found to be suitab le for the study of TMHs in IMP. (C) 1996 John Wiley & Sons, Inc.