NAGPKin: Nucleation-and-growth parameters from the kinetics of protein phase separation

Author:

Sárkány Zsuzsa12,Figueiredo Francisco12,Macedo-Ribeiro Sandra12,Martins Pedro M.12ORCID

Affiliation:

1. Biomolecular Structure and Function Group, IBMC – Instituto de Biologia Molecular e Celular, Porto 4200-135, Portugal

2. i3S – Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Porto 4200-135, Portugal

Abstract

The assembly of biomolecular condensate in eukaryotic cells and the accumulation of amyloid deposits in neurons are processes involving the nucleation and growth (NAG) of new protein phases. To therapeutically target protein phase separation, drug candidates are tested in in vitro assays that monitor the increase in the mass or size of the new phase. Limited mechanistic insight is, however, provided if empirical or untestable kinetic models are fitted to these progress curves. Here we present the web server NAGPKin that quantifies NAG rates using mass-based or size-based progress curves as the input data. A report is generated containing the fitted NAG parameters and elucidating the phase separation mechanisms at play. The NAG parameters can be used to predict particle size distributions of, for example, protein droplets formed by liquid-liquid phase separation (LLPS) or amyloid fibrils formed by protein aggregation. Because minimal intervention is required from the user, NAGPKin is a good platform for standardized reporting of LLPS and protein self-assembly data. NAGPKin is useful for drug discovery as well as for fundamental studies on protein phase separation. NAGPKin is freely available (no login required) at https://nagpkin.i3s.up.pt .

Publisher

American Society for Cell Biology (ASCB)

Subject

Cell Biology,Molecular Biology

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