title: Relative Binding Affinities of Monolignols to Horseradish Peroxidase.
abstract: Monolignol binding to the peroxidase active site is the first step in lignin polymerization in plant cell walls. Using molecular dynamics, docking, and free energy perturbation calculations, we investigate the binding of monolignols to horseradish peroxidase C. Our results suggest that p-coumaryl alcohol has the strongest binding affinity followed by sinapyl and coniferyl alcohol. Stacking interactions between the monolignol aromatic rings and nearby phenylalanine residues play an important role in determining the calculated relative binding affinities. p-Coumaryl and coniferyl alcohols bind in a pose productive for reaction in which a direct H-bond is formed between the phenolic -OH group and a water molecule (W2) that may facilitate proton transfer during oxidation. In contrast, in the case of sinapyl alcohol there is no such direct interaction, the phenolic -OH group instead interacting with Pro139. Since proton and electron transfer is the rate-limiting step in monolignol oxidation by peroxidase, the binding pose (and thus the formation of near attack conformation) appears to play a more important role than the overall binding affinity in determining the oxidation rate.
authors.affiliation: UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory , Oak Ridge, Tennessee 37831, United States.|Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee , Knoxville, Tennessee 37996, United States.
authors.forename: Amandeep K
authors.initials: AK
authors.lastname: Sangha
authors.affiliation: UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory , Oak Ridge, Tennessee 37831, United States.
authors.forename: Loukas
authors.initials: L
authors.lastname: Petridis
authors.affiliation: UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory , Oak Ridge, Tennessee 37831, United States.|Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee , Knoxville, Tennessee 37996, United States.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: UT/ORNL Center for Molecular Biophysics, Oak Ridge National Laboratory , Oak Ridge, Tennessee 37831, United States.|Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee , Knoxville, Tennessee 37996, United States.
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Smith
mesh_terms: D020134:Catalytic Domain; D003373:Coumaric Acids; D006735:Horseradish Peroxidase / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D010084:Oxidation-Reduction; D010636:Phenols / Q000737:chemistry / Q000378:metabolism*; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism; D010666:Phenylpropionates / Q000737:chemistry / Q000378:metabolism*; D011422:Propionates / Q000737:chemistry / Q000378:metabolism*; D011522:Protons; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D003373:Coumaric Acids; D010636:Phenols; D010666:Phenylpropionates; D011422:Propionates; D011522:Protons; D014867:Water; D010649:Phenylalanine; C496130:sinapyl alcohol; C010559:coniferyl alcohol; D006735:Horseradish Peroxidase; C495469:p-coumaric acid