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Strain energy in enzyme–substrate binding: An energetic insight into the flexibility versus rigidity of enzyme active site.
- Source :
- Computational & Theoretical Chemistry; Sep2012, Vol. 995, p17-23, 7p
- Publication Year :
- 2012
-
Abstract
- Abstract: Elucidating the structural properties of enzyme active site is fundamentally important for our understanding of the reaction mechanism and biochemical implication underlying enzyme catalysis. Instead of previous efforts that mainly concentrated on the structural change and atomic motion of enzyme system upon substrate binding, we herein dedicate our focuses to the energetic aspect of enzyme–substrate binding. In this study, 15 structure-known, functionally diverse enzyme–substrate complexes are retrieved from the Protein Data Bank (PDB) and then the strain energies both in enzyme and in substrate as well as the energetic contributions from nonbonded interaction and desolvation effect due to binding are calculated by using a mixed scheme of hybrid QM/MM, sophisticated DFT theory, and empirical PB/SA analysis. It is shown that the derived energy terms are well compatible to each other and their combination exhibits a good agreement with experimentally measured affinity. In addition, the strain energy appears to confer specificity for enzyme–substrate complex, whereas the stability of the complex is primarily dominated by nonbonded and desolvation facets. More importantly, although from the structural point of view the enzyme active site only bears a slight conformational change as compared to substrate molecule in binding, the strain energy in former is substantially greater than that in latter, implying a mixed feature of significant rigidity and also some flexibility in enzyme active site. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 2210271X
- Volume :
- 995
- Database :
- Supplemental Index
- Journal :
- Computational & Theoretical Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 78545927
- Full Text :
- https://doi.org/10.1016/j.comptc.2012.06.017