TY - JOUR

T1 - Fragmentation-Based Decomposition of a Metalloenzyme–Substrate Interaction: A Case Study for a Lytic Polysaccharide Monooxygenase

AU - Hellmers, Janine

AU - Hedegård, Erik Donovan

AU - König, Carolin

N1 - Funding Information: C.K. acknowledges support from the Deutsche Forschungsgemeinschaft (DFG) through the Emmy Noether Young Group Leader Programme (Project KO 5423/1-1). E.D.H. thanks The Villum Foundation, Young Investigator Program (Grant No. 29412), the Swedish Research Council (Grant No. 2019-04205), and Independent Research Fund Denmark (Grant No. 0252-00002B) for support.

PY - 2022/7/28

Y1 - 2022/7/28

N2 - We present a novel decomposition scheme for electronic interaction energies based on the flexible formulation of fragmentation schemes through fragment combination ranges (FCRs; J. Chem. Phys., 2021, 155, 164105). We devise a clear additive decomposition with contribution of nondisjoint fragments and correction terms for overlapping fragments and apply this scheme to the metalloenzyme-substrate complex of a lytic polysaccharide monooxygenase (LPMO) with an oligosaccharide. By this, we further illustrate the straightforward adaptability of the FCR-based schemes to novel systems. Our calculations suggest that the description of the electronic structure is a larger error source than the fragmentation scheme. In particular, we find a large impact of the basis set size on the interaction energies. Still, the introduction of three-body interaction terms in the fragmentation setup improves the agreement to the supermolecular reference. Yet, the qualitative results for the decomposition scheme with two-body terms only largely agree within the investigated electronic-structure approaches and basis sets, which are B97-3c, DFT (TPSS and B3LYP), and MP2 methods. The overlap contributions are found to be small, allowing analysis of the interaction energy into individual amino acid residues: We find a particularly strong interaction between the substrate and the LPMO copper active site.

AB - We present a novel decomposition scheme for electronic interaction energies based on the flexible formulation of fragmentation schemes through fragment combination ranges (FCRs; J. Chem. Phys., 2021, 155, 164105). We devise a clear additive decomposition with contribution of nondisjoint fragments and correction terms for overlapping fragments and apply this scheme to the metalloenzyme-substrate complex of a lytic polysaccharide monooxygenase (LPMO) with an oligosaccharide. By this, we further illustrate the straightforward adaptability of the FCR-based schemes to novel systems. Our calculations suggest that the description of the electronic structure is a larger error source than the fragmentation scheme. In particular, we find a large impact of the basis set size on the interaction energies. Still, the introduction of three-body interaction terms in the fragmentation setup improves the agreement to the supermolecular reference. Yet, the qualitative results for the decomposition scheme with two-body terms only largely agree within the investigated electronic-structure approaches and basis sets, which are B97-3c, DFT (TPSS and B3LYP), and MP2 methods. The overlap contributions are found to be small, allowing analysis of the interaction energy into individual amino acid residues: We find a particularly strong interaction between the substrate and the LPMO copper active site.

UR - http://www.scopus.com/inward/record.url?scp=85135380293&partnerID=8YFLogxK

U2 - 10.1021/acs.jpcb.2c02883

DO - 10.1021/acs.jpcb.2c02883

M3 - Article

VL - 126

SP - 5400

EP - 5412

JO - The Journal of Physical Chemistry B

JF - The Journal of Physical Chemistry B

SN - 1520-6106

IS - 29

ER -