Modeling lipid nanoparticles: Self-assembly and apparent pKa calculation
Abstract:
The application of lipid nanoparticles (LNPs) for the delivery of nucleic acids to address various health conditions is an active area of research and development. However, the limited understanding of the relationships between composition, structure, and performance hinders innovation, mainly due to the limited structural information that can be easily determined by experiment.
In this webinar, we will introduce Schrödinger’s coarse-grained simulation technology that can simulate the formation of LNP structures from a random mixture. This model enables structure-based design of LNPs by correctly reproducing many known structural features and some key behaviors (e.g. bleb formation as a function of pH) of LNP formulations. Another key aspect of LNP formulation is the design or selection of ionizable lipids (ILs) with appropriate apparent pKa values. We will present a structure-based, atomistic simulation technology for calculating formulation-specific apparent IL pKa values, which is designed to elucidate the factors which influence the apparent pKa and aid in IL selection.
Webinar Highlights:
- Simulation of the formation of LNP structures using coarse-grained molecular dynamics (MD) modeling technology
- Calculation of apparent pKa values of ILs via a structure-based, computational methodology
- Overview of Schrödinger’s computational solutions for understanding self-assembly and structural properties of LNPs
Our Speaker
John Shelley
Fellow, Schrödinger
John earned a MSc from the University of Waterloo in theoretical chemistry and a PhD from the University of Pennsylvania in computational chemistry. Following post-doctoral research in computational chemistry at the University of British Columbia, he worked for Procter & Gamble studying surfactant structures in solution. For the last 23 years, John has worked for Schrödinger, LLC, as a scientific software developer and a research scientist, managing a number of products including the Materials Science Coarse-Grained product. John has focused on computer modeling of drug formulations for much of the last 8 years.