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A density functional theory study on peptide bond cleavage at aspartic residues: direct vs cyclic intermediate hydrolysis

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Abstract

In this work, peptide bond cleavages at carboxy- and amino-sides of the aspartic residue in a peptide model via direct (concerted and step-wise) and cyclic intermediate hydrolysis reaction pathways were explored computationally. The energetics, thermodynamic properties, rate constants, and equilibrium constants of all hydrolysis reactions, as well as their energy profiles were computed at the B3LYP/6-311++G(d,p) level of theory. The result indicated that peptide bond cleavage of the Asp residue occurred most preferentially via the cyclic intermediate hydrolysis pathway. In all reaction pathways, cleavage of the peptide bond at the amino-side occurred less preferentially than at the carboxy-side. The overall reaction rate constants of peptide bond cleavage of the Asp residue at the carboxy-side for the assisted system were, in increasing order: concerted < step-wise < cyclic intermediate.

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Acknowledgments

This research work was supported financially by The Thailand Research Fund, co-funded by The Commission of Higher Education and The Faculty of Engineering, Rajamangala University of Technology Isan, Khonkaen campus through the young academic research grant no. MRG5380243 to W.S., which is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Engineering, Rajamangala University of Technology Isan, Khonkaen Campus, Srichan Road, Naimuang, Muang District, Khonkaen, 40000, Thailand

    Wichien Sang-aroon

  2. Integrated Nanotechnology Research Center, Department of Physics, Faculty of Science, Khon Kaen University, Khonkaen, 40002, Thailand

    Vittaya Amornkitbamrung

  3. Supramolecular Chemistry Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Phyathai Road, Pathumwan, Bangkok, 10320, Thailand

    Vithaya Ruangpornvisuti

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  1. Wichien Sang-aroon
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  2. Vittaya Amornkitbamrung
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  3. Vithaya Ruangpornvisuti
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Correspondence to Wichien Sang-aroon.

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Sang-aroon, W., Amornkitbamrung, V. & Ruangpornvisuti, V. A density functional theory study on peptide bond cleavage at aspartic residues: direct vs cyclic intermediate hydrolysis. J Mol Model 19, 5501–5513 (2013). https://doi.org/10.1007/s00894-013-2054-y

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  • DOI: https://doi.org/10.1007/s00894-013-2054-y

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