title: Molecular dynamics simulations of peptides from the central domain of smooth muscle caldesmon.
abstract: The central domain of smooth muscle caldesmon contains a highly charged region consisting of ten 13-residue repeats. Experimental evidence obtained from the intact protein and fragments thereof suggests that this entire region forms a single stretch of stable alpha-helix. We have carried out molecular dynamics simulations on peptides consisting of one, two and three repeats to examine the mechanism of alpha-helical stability of the central domain at the atomic level. All three peptides show high helical stability on the timescale of the MD simulations. Deviations from alpha-helical structure in all the simulations arise mainly from the formation of long stretches of pi-helix. Interconversion between alpha-helical and pi-helical conformations occurs through insertion of water molecules into alpha-helical hydrogen bonds and subsequent formation of reverse turns. The alpha-helical structure is stabilized by electrostatic interactions (salt bridges) between oppositely charged sidechains with i,i+4 spacings, while the pi-helix is stabilized by i,i+5 salt bridge interactions. Possible i,i+3 salt bridges are of minor importance. There is a strong preference for salt bridges with a Glu residue N-terminal to a basic sidechain as compared to the opposite orientation. In the double and triple repeat peptides, strong i,i+4 salt bridges exist between the last Glu residue of one repeat and the first Lys residue of the next. This demonstrates a relationship between the repetitive nature of the central domain sequence and its ability to form very long stretches of alpha-helical structure.
authors.affiliation: Department of Biological Sciences, Structural Biology Research Group, University of Calgary, 2500 University Dr NW, Calgary, Canada, T2N 1N4.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Shepherd
authors.forename: David
authors.initials: D
authors.lastname: van der Spoel
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Vogel
mesh_terms: D002148:Calmodulin-Binding Proteins / Q000737:chemistry*; D003198:Computer Simulation; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009130:Muscle, Smooth / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D014867:Water / Q000737:chemistry
chemical_list: D002148:Calmodulin-Binding Proteins; D010455:Peptides; D014867:Water