The research project is about the multiscale and multiphase molecular dynamics of intrinsically disordered proteins and proteinaceous liquid droplets.
The goal of the project is to perform systematic studies of single- and many-chain IDPs through a combination of coarse-
grained and all-atom simulations to understand the mechanisms of aggregation and structural biases. The focus of the research will be on proteins related either to neurodegeneration (alpha-
synuclein, tau) or with the memory consolidations (hCPEB3, Orb2). The ultimate goal of the research involving the coarse-
grained model is to study systems of many IDPs, including the proteinaceous droplets. The droplets arise under the conditions of large molecular densities through the liquid-
liquid separation. This results in compartmentalization into droplets that are necessary for the organization of vital processes.
Examples include stress bodies, P-granules, nucleoli signaling complexes, and centrosomes. These so called membraneless organelles typically consist of many proteins and nucleic acids that are combined at a higher density than in the surrounding fluid, but they may also consist of just one kind of IDPs, especially in in vitro studies.
The surface tension involved in the phase separation is generally small. The droplets undergo shape fluctuations and may combine through fusion.
The purpose of the research is to understand the properties of the droplets consisting of one kind of proteins, in collaboration with biologists in Madrid.
In particular, the main goal is to calculate the coexistence curves and the fluid parameters (surface tension, viscosity) for droplets made of different IDPs.
Most of the studies will involve the in-house coarse-grained molecular dynamics package. Another possible goal will be to generalize the package to enable studies of protein-RNA systems.