Three-dimensional structure of proteins determined by molecular dynamics with interproton distance restraints: application to crambin.

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Abstract
Model calculations are performed to evaluate the utility of molecular dynamics with NMR interproton distance restraints for determining the three-dimensional structure of proteins. The system used for testing the method is the 1.5-.ANG. resolution crystal structure of crambin (a protein of 46 residues) from which a set of 240 approximate interproton distances of less than 4 .ANG. are derived. The convergence properties of the method are examined by using different dynamics protocols and starting from two initial structures; ones is a completely extended .beta.-strand, and the other has residues 7-19 and 23-30 in the form of .alpha.-helices (as in the crystal structure) with the remaining residues in the form of extended .beta.-strands. In both cases global and local convergence to the correct final structure is achieved with rms atomic differences between the restrained dynamics structures and the crystal structure of 1.5-2.1 .ANG. for the backbone atoms and 2.1-2.8 .ANG. for all atoms; the averaged structure has backbone and all atom rms deviations of 1.3 and 1.9 .ANG., respectively. Further, it is shown that a restrained dynamics structure with significantly larger deviations (i.e., 5.7 .ANG. for the backbone atoms) can be characterized as incorrect, independent of a knowledge of the crystal structure.