Erik Donovan Hedegård
Postdoctoral fellow
Estimating the accuracy of calculated electron paramagnetic resonance hyperfine couplings for a lytic polysaccharide monooxygenase
Author
Summary, in English
Lytic polysaccharide monooxygenases (LPMOs) are enzymes that bind polysaccharides followed by an (oxidative) disruption of the polysaccharide surface, thereby boosting depolymerization. The binding process between the LPMO catalytic domain and polysaccharide is key to the mechanism and establishing structure-function relationships for this binding is therefore crucial. The hyperfine coupling constants (HFCs) from EPR spectroscopy have proven useful for this purpose. Unfortunately, EPR does not provide direct structural data and therefore the experimental EPR parameters have to be supported with parameters calculated with density functional theory. Yet, calculated HFCs are extremely sensitive to the employed computational setup. Using the LPMO Ls(AA9)A catalytic domain, we here quantify the importance of several choices in the computational setup, ranging from the use of specialized basis, the underlying structures, and the employed exchange-correlation functional. We show that specialized basis sets are an absolute necessity, and also that care has to be taken in the optimization of the underlying structure: only by allowing large parts of the protein around the active site to structurally relax could we obtain results that uniformly reproduced experimental trends. We compare our results to previously published X-ray structures and experimental HFCs for Ls(AA9)A as well as to recent experimental/theoretical results for another (AA10) family of LPMOs.
Department/s
- Computational Chemistry
Publishing year
2021
Language
English
Pages
555-567
Publication/Series
Computational and Structural Biotechnology Journal
Volume
19
Document type
Journal article
Publisher
Research Network of Computational and Structural Biotechnology
Topic
- Biological Sciences
Keywords
- DFT
- EPR
- LPMO
- QM/MM
Status
Published
ISBN/ISSN/Other
- ISSN: 2001-0370