F5.medium.gifIntrinsically disorder proteins (IDPs) are an important class of proteins. Traditionally, the application of Martini to study IDPs has been limited due to the constraints in 2ndary structure imposed by an elastic network. However, the use of Go-potentials [1] as well as the use of SAXS constraints [2] offers more possibilities to capture the broad range of configurations characteristic of IDPs.

Related to the ability to simulate IDPs comes the potential to simulate liquid-lquid phase separation (LLPS) of a variety of (bio)polymers. LLPS is gaining a lot of attention lately as it is believed to underly formation of membraneless organelles in the cell. The first examples of LLPS with Martini are starting to appear in the literature [3-7], with many more expected to follow.

[1] A.B. Poma, M. Cieplak, P.E Theodorakis. Combining the MARTINI and Structure-Based Coarse-Grained Approaches for the Molecular Dynamics Studies of Conformational Transitions in Proteins. J. Chem. Theory Comput. 13:1366–1374, 2017.

[2] A.H. Larsen, Y. Wang, S. Bottaro, S. Grudinin, L. Arleth, K. Lindorff-Larsen. Combining molecular dynamics simulations with small-angle X-ray and neutron scattering data to study multi-domain proteins in solution. PLoS Comput. Biol.16:e1007870, 2020.

[3] D. Priftis, M. Tirrell. Phase behaviour and complex coacervation of aqueous polypeptide solutions. Soft Matter 8:9396–9405, 2012.

[4] N.M. Milkovic, F.E. Thomasen, et al. Interplay of folded domains and the disordered low-complexity domain in mediating hnRNPA1 phase separation. BioRxiv, 2020. link

[5] T.J. Welsh, G. Krainer, J.R. Espinosa et al. Surface electrostatics govern the emulsion stability of biomolecular condensates. BioRxiv, 2020.

[6] Z. Benayad, S. von Bülow, L.S. Stelzl, G. Hummer. Simulation of FUS protein condensates with an adapted coarse-grained model. BioRxiv, 2020.

[7] M. Tsanai, P.W.J.M. Frederix, C.F.E. Schroer, P.C.T. Souza, S.J. Marrink. Coacervate formation studied by explicit solvent coarse-grain molecular dynamics with the Martini model. Chemical Science, 2021.