A geometrical constraint approach for reproducing the native backbone conformation of a protein

It is known that the backbone conformation of a protein can be reproduced with precision once a correct contact map (two‐dimensional representation showing residue pairs in contact) is given as geometrical constraints. There is, however, no way to infer the correct contact map for a protein of unknown structure. We started with one‐dimensional constraints using the quantity N14 (the number of neighboring residues within the radius of 14 Å). Since the plot of N14 along a chain shows a good correlation with the corresponding amino acid sequence, the N14 profile obtained from the X‐ray structure is predictable from the sequence. Construction of backbone conformations under a given N14 profile was carried out in the following two steps: (1) a contact map from the N14 profile was produced by taking the product of N14 values of every two residues; (2) backbone conformations were generated by applying the distance geometry technique to distance constraints given by the contact map. If present, disulfide bonds in a protein, as well as the secondary structure, were treated as additional constraints, and both cases with or without the additional information were examined. The method was tested for 11 proteins of known structure, and the results indicated that the reproduced conformation was fairly good, using an X‐ray structure for comparison, for small proteins of less than 80 residues long. The basic assumption and effectiveness of the present method were compared with those of previous studies employing the geometrical constraint approach. It has become clear that the specific, one‐dimensional information (e.g., N14 profile) is more effective than nonspecific, two‐dimensional constraints, such as average interresidue distances between particular types of amino acids. © 1993 Wiley‐Liss, Inc.