APPLICATION OF DISTANCE GEOMETRY TO PROTEIN TERTIARY STRUCTURE CALCULATIONS

A general approach to the problem of molecular conformation is advanced. We describe a formalism that permits experimental and theoretical information to be incorporated into a set of upper and lower bounds on intramolecular distances. Structures (conformations) meeting these bounds can be readily generated and compared with each other. To illustrate the use of the method, we have employed a simple “firehose” model for protein folding to predict the long‐range hydrophobic interactions in a small protein: pancreatic trypsin inhibitor. Models of this type lead to the proper hairpin turns and a reasonable set of long‐range contacts for this protein. Application of the distance geometry method then yields backbone conformations with errors of 4–8 Å compared to the native structure. We discuss both the merits and shortcomings of the firehose model and the relation between distance geometry and energy minimization techniques. Copyright © 1979 John Wiley & Sons, Inc.