Theoretical study of the contribution of aromatic side chains to the circular dichroism of basic bovine pancreatic trypsin inhibitor

Biochemistry ◽  
1989 ◽  
Vol 28 (21) ◽  
pp. 8609-8613 ◽  
Author(s):  
Mark C. Manning ◽  
Robert W. Woody
Keyword(s):  
Circular Dichroism ◽  
Trypsin Inhibitor ◽  
Theoretical Study ◽  
Bovine Pancreatic Trypsin Inhibitor ◽  
Side Chains ◽  
Pancreatic Trypsin Inhibitor ◽  
Circular Dichroïsm ◽  
Aromatic Side Chains

scholarly journals Free Energy Landscape and Rate Estimation of the Aromatic Ring Flips in Basic Pancreatic Trypsin Inhibitor Using Metadynamics

2021 ◽  
Author(s):  
Pär Söderhjelm ◽  
Mandar Kulkarni
Keyword(s):  
Free Energy ◽  
Trypsin Inhibitor ◽  
Side Chain ◽  
Side Chains ◽  
Aromatic Residues ◽  
Basic Pancreatic Trypsin Inhibitor ◽  
Pancreatic Trypsin Inhibitor ◽  
Energy Surfaces ◽  
Aromatic Side Chains

Aromatic side-chains (phenylalanine and tyrosine) of a protein flip by 180° around the Cβ-Cγ axis (χ2 dihedral of side-chain) producing two symmetry-equivalent states. The ring-flip dynamics act as an NMR probe to understand local conformational fluctuations. Ring-flips are categorized as slow (ms onwards) or fast (ns to near ms) based on timescales accessible to NMR experiments. In this study, we investigated the ability of the infrequent metadynamics approach to discriminate between slow and fast ring-flips for eight individual aromatic side-chains (F4, Y10, Y21, F22, Y23, F33, Y35, F45) of basic pancreatic trypsin inhibitor (BPTI). Well-tempered metadynamics simulations were performed to observe ring-flipping free energy surfaces for all eight aromatic residues. The results indicate that χ2 as a standalone collective variable (CV) is not sufficient to classify fast and slow ring-flips. Most of the residues needed χ1 (N−Cχα) as a complementary CV, indicating the importance of librational motions in ring-flips. Multiple pathways and mechanisms were observed for residues F4, Y10, and F22. Recrossing events are observed for residues F22 and F33, indicating a possible role of friction effects in the ring-flipping. The results demonstrate the successful application of the metadynamics based approach to estimate ring-flip rates of aromatic residues in BPTI and identify certain limitations of the approach.

Circular dichroism studies of barnase and its mutants: Characterization of the contribution of aromatic side chains

Biochemistry ◽  
1993 ◽  
Vol 32 (39) ◽  
pp. 10303-10313 ◽  
Author(s):  
Stephane Vuilleumier ◽  
Javier Sancho ◽  
Ron Loewenthal ◽  
Alan R. Fersht
Keyword(s):  
Circular Dichroism ◽  
Side Chains ◽  
Circular Dichroïsm ◽  
Aromatic Side Chains

scholarly journals Characterization of the distribution of internal motions in the basic pancreatic trypsin inhibitor using a large number of internal NMR probes

1983 ◽  
Vol 16 (1) ◽  
pp. 1-57 ◽  
Author(s):  
Gerhard Wagner
Keyword(s):  
Trypsin Inhibitor ◽  
Side Chains ◽  
Internal Motions ◽  
Wide Range ◽  
Basic Pancreatic Trypsin Inhibitor ◽  
Pancreatic Trypsin Inhibitor ◽  
External Conditions ◽  
Nmr Techniques ◽  
Aromatic Side Chains

The experimental observations described in this article indicated that a distribution of many different fluctuations is present in a globular protein. These fluctuations were characterized by observation of many natural internal probes such as the labile peptide protons and the aromatic side chains. The conditions which are necessary to get reactions of the internal probes have been discussed in detail. The structural interpretation of the data was facilitated by the development and the use of new NMR techniques which provided the identification of the resonances of all the labile peptide protons. With NOE measurements a distinction between correlated and uncorrelated exchange events was obtained. This enabled us to elucidate the exchange mechanism over a wide range of p2H and temperature and to classify different subsets of fluctuations with respect to their lifetimes. It was further demonstrated that a change of external conditions such as temperature, p2H or pressure can change the distribution of fluctuations in the protein. The mechanisms responsible for rotation of internal aromatic side chains were also found to change with temperature, and mechanistic aspects of these fluctuations were discussed.

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