in silico: Disordered Proteins in Cells and Bio-Inspired Materials – DiPCaM

Phase separation of intrinsically disordered proteins underlines the formation of biomolecular condensates in diverse organisms, which play an important role in physiological functions. Such condensates are also seen as promising candidates in various applications, including drug delivery and tissue design, where the biocompatibility of the material is vital. Thus, the characterisation of the phase behaviour of disordered proteins and their derivatives is essential for our understanding of biological processes as well as important for the design of polymeric materials with specific properties. Here, we propose to develop a computational framework that will enable us to investigate protein and protein-based polymer self-assemblies through coarse-grained simulations. The novelty of our approach will lie in the quantitative inclusion of temperature dependence and larger chemical space into the well-established Martini force field. Relying on atomistic simulations, experimental data for a wide temperature range, and advanced multi-configurational coarse-graining methods, we will remedy its current limitations. Next, we will investigate how changes in the protein sequence, namely, charge distribution along the sequence and hydrophobicity of the residues, affect the phase behaviour of the system. Finally, we will disentangle the role of folded and disordered domains in the formation of condensates for two protein families linked to neurodegenerative diseases through large-scale molecular dynamics simulations.