Title:	Advanced computed simulations for encapsulated proteins and nucleic acids in lipid sponge phase
DNr:	SNIC 2021/5-85
Project Type:	SNIC Medium Compute
Principal Investigator:	Tommy Nylander <tommy.nylander@fkem1.lu.se>
Affiliation:	Lunds universitet
Duration:	2021-03-01 – 2022-03-01
Classification:	10603 10304 10399
Homepage:	https://www.researchgate.net/profile/Tommy_Nylander
Keywords:

Abstract

Sponge phase lipid nano-particles (LNPs) for encapsulation of proteins and nucleic acids are of a high interest in a modern pharmaceutical industry. Nowadays, such LNPs can become even competitive against the formulations of modern vaccines, including covid-19 vaccine, due to their high stability. These therapeutics are very challenging for structural characterization due to their complexity, disorder and large sizes. For instance, each LNP can contain hundreds of thousands of large lipid molecules what can result in heavy and even non-converging calculations by crystallographic software using direct methods. Moreover, experimental data is ambiguous for such systems which requires to be explained by computer simulations on various levels: from atomistic to meso-scale as well as by free-energy calculations. In this project multi-scale molecular dynamics (MD) simulations and advanced sampling techniques in combination with small-angle scattering and neutron spin echo techniques will be used for structural refinement and investigation of pharmacological properties of therapeutic sponge phase LNPs. All-atom MD simulations will provide us more detailed structural information on smaller scale while simulations on coarse-grained level will reveal dynamics of large LNPs loaded with proteins and nucleic acids. Advanced sampling techniques can give ideas about the encapsulation process from the thermodynamics point of view. Furthermore, newly derived models will become available for the whole computational community in order to help to develop more advanced medicines against cancer, Alzheimer's, Parkinson's and many other diseases as well as create a better quality lactose-free products. Gromacs software and plumed is seen as a powerful tool for performing the task on the latest high-performance computing systems at the National Supercomputer Center. We also are going to develop own software for the structural refinement.