Protein Backbone Structure Research Articles

Statistical mechanical treatment of protein conformation. 6. Elimination of empirical rules for prediction by use of a high-order probability. Correlation between the amino acid sequences and conformations for homologous neurotoxin proteins.

One-dimensional short-range interaction models for specific-sequence copolymers of amino acids have been developed in this series of papers. In this paper, a general method for predicting protein conformation (that is based on a one-dimensional short-range interaction model, and eliminates the need for the empirical rules introduced in papers III and IV) is described. The present method involves the use of conformational (or conformational-sequence) probabilities of higher order than the first- or second-order probabilities used in papers IV and V, i.e., it treats a sequence of any number of residues; it thus alters the predictive methods that involved empirical rules in papers III and IV, and low-order (first- or second-order) probabilities in papers IV and V. The general method is applied here to the prediction of the backbone conformations of proteins, using the three-state model [helical (h), extended (epilson), and other coil (c) states] proposed in the theoretical formulation of paper II. The statistical weights in the three-state model are evaluated from the atomic coordinates of the x-ray structures of 26 proteins. The conformational-sequence probabilities (taken for three consecutive residues for numerical computation in this paper) are calculated for all possible triads (i.e., for all possible combinations of the three states, h, epilson, and c for each residue) for bovine pancreatic trypsin inhibitor and clostridial flavodoxin, in order to select the most probable conformations of these proteins. The predicted results for these proteins are compared to those predicted in paper III and to those observed experimentally. The method is applied further to the prediction of the backbone structures of homologous neurotoxin proteins whose amino acid sequences are known but whose x-ray structures are not. The effects of variation in the amino acid sequence on the conformations of the backbones are discussed from the point of view of the homologies in the amino acid sequences of 19 neurotoxins. Application of the present general predictive method to a four- and a multistate model is also described.

Possible three-dimensional models for the polypeptide backbone structure of alamethicin

Based on an empirical procedure of predicting polypeptide backbone structures of proteins, an attempt was made to construct possible three-dimensional models for the secondary structure of alamethicin. Two chemical properties were used to limit the number of possible models: the presence of seven to eight α-aminoisobutyric acid residues whose conformations were quite restricted, and a covalent bond between the proline residue at position 1 and the glutamic acid residue at position 17. The predicted structures appear very compact and show features in agreement with circular dichroism and optical rotatory dispersion results, nuclear magnetic resonance measurements, and compressed monolayer studies.