Calmodulin (CaM) is a relatively small (148 residues) dumbbell-shaped protein of exceptional versatility that regulates the activity of a large number of cellular proteins. An example of aCaM-activated protein is myosin light chain kinase which regulates smooth muscle contraction [80]. We are especially interestedin the conformation of the central ff-helix of CaM, which is intactin the crystal structure [80], but has been found to dissolve in solution [80, 81]. The crystal structure of CaM [80] has been placedin a solvent sphere of 44 A radius, and six Cl- and 22 Na+ ionswere included to neutralize the system and model a 150 mM salt concentration, for a total simulation size of 32,867 atoms.Lessextensive calculations (see [82] for a review) were carried out earlier by our collaborators at CUNY. We have completed 3 ns of simulation time with the program X-PLORon the Cray T3D atthe Pittsburgh Supercomputing Center. The simulation reveals large-scale domain movements on the nanosecond timescale upon relaxation. The central tethering helix bends and unwinds near residue Arg74. The observed flexibility of the long central tethering helix allows CaM to have different binding conformations available for the recognition of various target peptides.
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