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Effects of distance constraints on macromolecular conformation. II. Simulation of experimental results and theoretical predictions

Havel, T.F., Crippen, G.M., Kuntz, I.D.
Biopolymers 1979 v.18 no.1 pp. 73-81
protein secondary structure, mathematical models, proteins, molecular conformation, prediction
By generating classes of random structures for trypsin inhibitor and carp myogen, each consistent with a given set of experimental or theoretical information, we have assessed the relative utility of various experiments and theories in deducing the conformation of macromolecules We compare the calculated structures with known x-ray coordinates and compute for each class an average error. Small errors mean that the experimental or theoretical constraints limit the structures to the vicinity of the crystal structure, whereas large errors show that the constraints permit a wide variety of tertiary conformations. We find the following points to hold true: (1) Qualitative information on all the distances, as might be obtained from the correct prediction of interresidue contacts, effectively determines the structure (error approximately 1 angstrom). (2) Quantitative information on a limited number of distances, as might be obtained from nmr or crosslinking experiments, significantly restricts the range of possible structures only when the number of distances given is comparable to the number of residues (error approximately 3 angstroms). (3) Quantitative information on the distances of each residue to the center of mass of the molecule, as might in part be obtained from solvent accessibility and solution x-ray studies, is not particularly restrictive by itself (error approximately 5 angstroms). (4) Complete qualitative local distance information, as might be obtained from secondary prediction and CD/ORD studies, is clearly consistent with a wide variety of tertiary structures (error approximately 7 angstroms).