# Lipid Nanoparticle Database towards structure-function modeling and data-driven design for nucleic acid delivery

## TL;DR

The paper introduces LNPDB, a database and tool for lipid nanoparticles, enabling better design of nucleic acid delivery systems through standardized data and simulations.

## Contribution

The novel contribution is the creation of LNPDB, a unified database and web tool for lipid nanoparticle data and modeling.

## Key findings

- LNPDB consolidates data for 19,528 lipid nanoparticles with standardized featurization.
- LNPDB supports molecular dynamics simulations and deep learning for predicting delivery performance.
- Structural features like bilayer stability correlate with LNP delivery effectiveness.

## Abstract

Lipid nanoparticles (LNPs) are the leading nonviral nucleic acid delivery technology, but LNP structure-function data remains fragmented and nonstandardized. Unlike protein engineering which is anchored by the centralized Protein Data Bank, the LNP field lacks a unified repository for systematic analysis. To address this, we develop Lipid Nanoparticle Database (LNPDB) (https://lnpdb.molcube.com), an integrated database and web tool that consolidates structural and functional data for 19,528 LNPs. LNPDB standardizes LNP featurization by encoding lipid composition, experimental methods, and functional results, and generates CHARMM force field files for constituent lipids to enable molecular dynamics simulations. LNPDB also supports future data contributions for continued growth. We examine the utility of LNPDB through two applications: advancing our deep learning model for predicting LNP delivery performance, and simulating bilayer dynamics to identify structural features – bilayer stability and critical packing parameter – that correlate with LNP delivery performance. Altogether, LNPDB provides the digital framework for LNP modeling and data-driven rational design.

This study introduces the Lipid Nanoparticle Database (LNPDB) and web tool that consolidates lipid nanoparticle structure-function data. LNPDB facilitates molecular dynamics and deep learning approaches to advance data-driven design for nucleic acid delivery.