Biophysical Society Thematic Meeting | Hamburg 2022

Biophysics at the Dawn of Exascale Computers

Poster Abstracts

4-POS Board 4 COARSE-GRAINED MODELS FOR INTRINSICALLY DISORDERED DOMAINS PORTED INTO GROMACS: HOW PHOSPHORYLATION SHIFTS IDP CONFORMATIONAL ENSEMBLES Camilo Aponte-Santamaría 1 ; Isabel Martin 1 ; Adel Iusupov 1,2,4 ; Frauke Gräter 1,3,4 ; 1 Heidelberg Institute for Theoretical Studies, Molecular Biomechanics Group, Heidelberg, Germany 2 University of Göttingen, Göttingen, Germany 3 Heidelberg University, Interdisciplinary Center for Scientific Computing, Heidelberg, Germany 4 Max Planck School Matter to Life, Heidelberg, Germany Determination of the dynamics of intrinsically disordered proteins (IDPs) is essential to understand their function. Although all-atom molecular dynamics (MD) simulations have enabled a quantitative monitoring of the dynamics of these types of proteins at an unprecedented and valuable level of detail, they are still limited to relatively small and individual IDPs. Several coarse-grained models have been recently proposed to efficiently and accurately simulate complete single IDP chains and IDP condensates. These models treat each aminoacid as one particle and involve non-bonded interactions which are different than the conventionally used- ones in standard biomolecular MD simulations. Implementations of these models exist in MD packages such as LAMMPS or HOOMD. Here, we report the port of three recent models HPS, CALVADOS, and MPIPI into the widely used MD software GROMACS. The port is applied to study the dynamics of the intrinsically disordered region of the inner centromere protein (INCENP), a part of the chromosome passenger complex playing a key role during mitosis. The disordered fragment of INCENP is about 440 aminoacids long and our coarse-grained simulations allowed us to systematically study the effect of the phosphorylation on this disordered region, backed up by all-atom simulations of individual short INCENP fragments (Martin, Aponte-Santamaría, et al. J Mol Biol. 434: 167387, 2022). Overall, we expect this port to complement other existing implementations of IDP coarse-grained models and to facilitate their use into a unifying MD framework within the GROMACS package.

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