Molecular Dynamics Simulations of Peptides from the Central Domain of Smooth Muscle Caldesmon

Craig M. Shepherd, David van der Spoel, Hans J. Vogel
2004 Journal of Biomolecular Structure and Dynamics  
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 α-helix. We have carried out molecular dynamics simulations on peptides consisting of one, two and three repeats to examine the mechanism of α-helical stability of the central domain at the atomic level. All three peptides show high
more » ... stability on the timescale of the MD simulations. Deviations from α-helical structure in all the simulations arise mainly from the formation of long stretches of π-helix. Interconversion between α-helical and π-helical conformations occurs through insertion of water molecules into α-helical hydrogen bonds and subsequent formation of reverse turns. The α-helical structure is stabilized by electrostatic interactions (salt bridges) between oppositely charged sidechains with i,i+4 spacings, while the π-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 α-helical structure.
doi:10.1080/07391102.2004.10506948 pmid:14692799 fatcat:fulodtvtqzfhrflowaj2zbpeyy