Nuclear Magnetic Resonance and Metadynamics Simulations Reveal the Atomistic Binding of l-Serine and O -Phospho-l-Serine at Disordered Calcium Phosphate Surfaces of Biocements.
Renny MathewBaltzar StevenssonMichael Pujari-PalmerChristopher S WoodPhillip R A ChiversChristopher D SpicerHélène AutefageMolly M StevensHåkan EngqvistMattias EdénPublished in: Chemistry of materials : a publication of the American Chemical Society (2022)
Interactions between biomolecules and structurally disordered calcium phosphate (CaP) surfaces are crucial for the regulation of bone mineralization by noncollagenous proteins, the organization of complexes of casein and amorphous calcium phosphate (ACP) in milk, as well as for structure-function relationships of hybrid organic/inorganic interfaces in biomaterials. By a combination of advanced solid-state NMR experiments and metadynamics simulations, we examine the detailed binding of O -phospho-l-serine (Pser) and l-serine (Ser) with ACP in bone-adhesive CaP cements, whose capacity of gluing fractured bone together stems from the close integration of the organic molecules with ACP over a subnanometer scale. The proximity of each carboxy, aliphatic, and amino group of Pser/Ser to the Ca 2+ and phosphate species of ACP observed from the metadynamics-derived models agreed well with results from heteronuclear solid-state NMR experiments that are sensitive to the 13 C- 31 P and 15 N- 31 P distances. The inorganic/organic contacts in Pser-doped cements are also contrasted with experimental and modeled data on the Pser binding at nanocrystalline HA particles grown from a Pser-bearing aqueous solution. The molecular adsorption is driven mainly by electrostatic interactions between the negatively charged carboxy/phosphate groups and Ca 2+ cations of ACP, along with H bonds to either protonated or nonprotonated inorganic phosphate groups. The Pser and Ser molecules anchor at their phosphate/amino and carboxy/amino moieties, respectively, leading to an extended molecular conformation across the surface, as opposed to an "upright standing" molecule that would result from the binding of one sole functional group.
Keyphrases
- solid state
- protein kinase
- aqueous solution
- water soluble
- magnetic resonance
- bone mineral density
- bone regeneration
- molecular dynamics simulations
- dna binding
- soft tissue
- binding protein
- molecular dynamics
- bone loss
- pseudomonas aeruginosa
- electronic health record
- cystic fibrosis
- postmenopausal women
- magnetic resonance imaging
- single cell
- computed tomography
- mass spectrometry
- big data
- monte carlo
- deep learning