Calculation of protein conformation as an assembly of stable overlapping segments: Application to bovine pancreatic trypsin inhibitor

Istvan Simon, Leslie Glasser, Harold A. Scheraga

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Conformations of bovine pancreatic trypsin inhibitor were calculated by assuming that the final structure as well as properly chosen overlapping segments thereof are simultaneously in low-energy (not necessarily the lowestemergy) conformational states. Therefore, the whole chain can be built up from building blocks whose conformations are determined primarily by short-range interactions. Our earlier buildup procedure was modified by taking account of a statistical analysis of known amino acid sequences that indicates that (here is nonrandom pairing of amino acid residues in short segments along the chain, and by carrying out energy minimization on only these segments and on the whole chain [without minimizing the energies of intermediate-size segments (29-30 residues long)]. Results of this statistical analysis were used to determine the variable sizes of the overlapping oligopeptide building blocks used in the calculations; these varied from tripeptides to octapeptides, depending on the amino acid sequence. Successive stages of approximations were used to combine the low-energy conformations of these building blocks in order to keep the number of variables in the computations to a manageable size. The calculations led to a limited number of conformations of the protein (only two different groups, with try similar structure within each group), most residues of which were in the same conformational state as in the native structure.

Original languageEnglish
Pages (from-to)3661-3665
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number9
DOIs
Publication statusPublished - 1991

Keywords

  • "Conformon"
  • Build-up procedure
  • Conformational energy calculations
  • Short-range interactions

ASJC Scopus subject areas

  • General

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