Title:	Binding of Biomolecules at Inorganic Phosphate Surfaces
DNr:	SNIC 2021/5-165
Project Type:	SNIC Medium Compute
Principal Investigator:	Mattias Edén <mattias.eden@mmk.su.se>
Affiliation:	Stockholms universitet
Duration:	2021-04-01 – 2022-04-01
Classification:	10402 10403
Homepage:	http://www.su.se/profiles/eden-1.187322
Keywords:

Abstract

In the SSF-funded project “Active Calcium Phosphate Cements”, we investigate calcium phosphate cements (CPCs) with bone adhesive properties for the next-generation bone implants. We have recently shown by advanced NMR experimentation that the bone adhesion of CPCs incorporating phosphoserine (Pser) may be predicted well from the amount of an amorphous cement component that involves an intimate binding between Pser and amorphous calcium phosphate (ACP) [1]. Molecular dynamics (MD) simulations utilizing metadynamics have revealed the details of the PSer adsorption, as well as for other small biomolecules (such as citrate) [2], on structurally disordered surfaces of calcium hydroxyapatite (HA), which is the mother structure of bone mineral. Our previous metadynamics simulations using the HA-surface preparation of ref. [3] offered significant improvement of the modeling accuracy relative to previous simulations that assumed periodic HA surfaces with a chemical surface speciation only relevant at an infinitely high pH value. In our future modeling studies, we will (1) examine the separate bearings on the molecular binding energy and the molecular conformation from the structural (dis)order at the surface, the inclusion/exclusion of OH groups, as well as the pH-dependent protonation states of the inorganic phosphate groups at the surface; (2) Perform simulations of molecular binding at fully amorphous calcium phosphate surfaces, to further improve the mimicking of the observed Pser/ACP component in the CPCs; (3) Make further developments and assessments of a new energy-analysis protocol introduced by us [2], which allows to separately studying the various contributions (functional groups and interaction types) to the binding energy of a biomolecule at an inorganic surface. References: [1] “Solid-State NMR Rationalizes the Bone-Adhesive Properties of Serine- and Phosphoserine-Bearing Calcium Phosphate Cements by Unveiling their Organic/Inorganic Interface”; R. Mathew M. Pujari-Palmer, H. Guo, Y. Yu, B. Stevensson, H. Engqvist, M. Edén, J. Phys. Chem. C, 124, 21512−21531 (2020) [2] “Metadynamics Simulations of the pH Dependent Adsorption of Phopshoserine and Citrate on Disordered Apatite Surfaces: What Interactions Govern the Molecular Binding?”; B. Stevensson, M. Edén, submitted [3] “Accurate Force Field Parameters and pH Resolved Surface Models for Hydroxyapatite to Understand Structure, Mechanics, Hydration, and Biological Interfaces”; T.-J. Lin, H. Heinz; J. Phys. Chem. C, 9, 4975−4992 (2016)