Modelling the structure and crystallisation of kidney stones

Urinary calculi (kidney stones) are a common ailment, effecting around 10% of the world's population, and the key chemical interactions relating to its crystallisation are not fully understood. A kidney stone is a solid lump, composed of crystals that have separated from urine, and built up on the inner surface of the kidney. A kidneys function is to filter blood of waste products and excess water, if too little water is available to dilute the waste products, the waste can stay in the kidney and form solid pieces of material. The build-up of these pieces form kidney stones which can vary in size, from the size of a grain of sand to a golf ball. There are three main types of kidney stone; calcium stones (calcium oxalate principally), struvite stones and uric acid stones. Moreover, kidney stones are often found complexed to organic matrices, such as proteins, and the fundamental chemistry underlying this observation is unknown.

This research will use first principles modelling to help to elucidate the crystallisation phenomena, and unravel the prevalent chemistry behind stone composition to, in a future sense, offer potential strategies for drug development and stone prevention. Crystal growth is either by aggregation or epitaxy, a process of orientated growth of one crystalline lattice over another. Aggregated particles can stick to the renal epithelium, and have the chance to grow into stones. This study will explore the chemical molecular interactions combinatorially, implicated in nucleation, focusing on ab initio molecular dynamics methods to understand the prevalent chemistry.

Explicitly, this project will use theoretical and computational chemistry approaches to explore the organic-inorganic interfacial interactions. The first steps of this study is to look into the mechanism of how kidney stones form, this is currently not well understood, potential methods include; molecular dynamics, accelerated molecular dynamics, metadynamics or QM/MM. Other avenues of interest could include looking into inhibitors (such as citrate) or accelerators of stone formation, what is the chemistry making this happen. Would the addition of a different anion species have any effect on the crystallisation of calcium oxalate. Do side chains have an influence on stone formation, what if we phosphorylate these. Could explore these interactions using a variation of computational methods such as; Density functional theory, molecular dynamics and QM/MM.