Dynamics of the aromatic amino acid residues in the globular conformation of the basic pancreatic trypsin inhibitor (BPTI) - II. Semi-empirical energy calculations

Robert Hetzel, Kurt Wüthrich, Johann Deisenhofer, Robert Huber

Research output: Contribution to journalArticle

53 Scopus citations

Abstract

The molecular conformation of the basic pancreatic trypsin inhibitor (BPTI) is known in considerable detail from both X-ray studies in single crystals and NMR studies in solution. The NMR experiments showed that the aromatic rings of the phenylalanyl and tyrosyl residues can undergo rapid rotational motions about the Cβ-Cγ bond. The present paper describes a model investigation of the mechanistic aspects of these intramolecular rotational motions. From calculations of the conformational energies for molecular species derived from the X-ray structure by rotations of individual aromatic rings, it was apparent that the rotational motions of the aromatics could only be understood in a flexible structure. Flexibility was simulated by allowing the protein to relax to an energetically favorable conformation for each of the different rotation states of the aromatic rings. It was then of particular interest to investigate how the perturbations caused by different rotation states of the aromatic rings were propagated in the protein structure. It was found that the rotation axes Cβ-Cγ were only slightly affected (Δχ1≲20°). The most sizeable perturbations are caused by through space interactions with nearby atoms, which move away from the ring center and thus release the steric hindrance opposing the rotational motions. The values for the energy barriers obtained from the energy minimization are of the same order of magnitude as those measured by NMR.

Original languageEnglish (US)
Pages (from-to)159-180
Number of pages22
JournalBiophysics of Structure and Mechanism
Volume2
Issue number2
DOIs
StatePublished - Jun 1 1976

Keywords

  • Conformational energy calculations
  • Molecular mechanics
  • Protein conformation
  • Proteinase inhibitor

ASJC Scopus subject areas

  • Medicine(all)

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