Title:	Binding of Biomolecules at Inorganic Phosphate and Silicate Surfaces
DNr:	SNIC 2019/3-682
Project Type:	SNIC Medium Compute
Principal Investigator:	Mattias Edén <mattias.eden@mmk.su.se>
Affiliation:	Stockholms universitet
Duration:	2020-01-01 – 2021-01-01
Classification:	10402 10403
Homepage:	http://www.su.se/profiles/eden-1.187322
Keywords:

Abstract

By combining results from atomistic MD simulations, DFT calculations, and NMR experiments, we will study the adsorption of phosphoserine (Pser) and other small biomolecules at the surface of calcium hydroxyapatite (HA), which is the mother structure of bone mineral. Phosphoserine (Pser) is an ester of serine and phosphoric acid, and is abundant in many proteins believed to initiate and regulate bone growth [1]. In the SSF-funded project “Active Calcium Phosphate Cements”, Pser-bearing calcium phosphate cements (CPCs) are investigated for the next-generation bone implants. After a mixture of calcium phosphates is injected in a bone/tooth void, it hardens into a HA-like cement, which strongly interfaces with the surrounding bone tissue. Including Pser in the cement makes it adhesive, so that it may be used to “glue” bone pieces together. Here we aim at improving the insight into the Pser/CPC interface by its selective experimental probing and by MD/DFT modeling. During the course of the SSF project, more recent investigations are in progress for using calcium silicate-based cements as a bone glue. Hence, the sought computer resources are in part required for completing those already outlined in our ongoing project, "Binding of Biomolecules at Inorganic Phosphate Surfaces" (SNIC 2018/3-601), as well as extended studies where we will examine the binding of Pser, citrate, and other small molecules on the surface of calcium silicate (CaSiO3). Moreover, advanced solid-state NMR experimentation on the Pser-bearing CPCs reveal that the organic/inorganic interface is largely amorphous. We will therefore also model the structure of amorphous calcium phosphate (ACP), as well as the incorporation of carbonate ions in its structure; the latter calculations are needed for an on-going project funded by the Calr Trygger Foundation (CTS 17:130). The modeling will mainly involve atomistic MD simulations incorporating meta-dynamics of a system with water, organic molecules, and the inorganic component; the latter involves the bulk and the surface of either HA or calcium silicate. Here we will explicitly account for the dependence of the surface speciation on the pH of the solution [2]; this is rarely considered in literature reports on similar calculations on related systems. The computations will explore the relative affinities/binding energies of the organic molecules at different crystallographic surfaces, locate their preferred orientation at the surface, and include the dependence of these parameters/properties on the pH and concentration. The MD simulations will be benchmarked against Car-Parrinello DFT calculations. The modeled results will be compared with data from advanced solid-state NMR experiments on CPC-Pser composites and model systems of nano-crystalline HA grown from solutions comprising each organic species. References: [1] A George, A Veis, Chem. Rev. 108, p4670 (2008) [2] T-J Lin, H Heinz, J. Phys. Chem C, 120, p4975 (2016)