SUNY at Albany
June 19-23, 2001
Calculated myosin motions with coarse-grained models
Elastic network models of proteins coarse-grained at the level of one point per residue have proven to yield the largest scale collective motions of proteins. The analysis utilized is similar to a normal mode analysis, of a set of highly coupled springs, where only the a-carbon atoms interact with others nearby ones, without any residue specificity or differentiation regarding sequence connectedness. Mathematically this involves inversion of the contact matrix that specifies the residues connected by the springs. We have applied this approach to myosin and are able to observe global motions of the protein. Myosin is a molecular motor that converts chemical energy into directed movement. According to the rotating crossbridge model, the movement of myosin is driven by a directed conformational change within the crossbridge that the motor protein forms with the actin filament. One particular interest is to understand the larger conformational changes of protein domains during this actomyosin cycle. Crystallographic structures of three conformations of the same myosin head, containing the motor domain and the lever arm, light chains included,(1141 residues) have been used for these calculations. The slowest modes obtained may indicate the types of transitions between the structures, as well as serve to identify the portions of the protein implicated in the conformational changes.
Isabelle Navizet and Robert Jernigan
Molecular Structure Section, Laboratory of Experimental and Computational Biology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, MSC 5677, Bethesda, MD 20892-5677,