Atomistic molecular dynamics simulations (aMDs) are limited in their ability to explore membrane-associated phenomena because of time-scale constraints. This limitation can be overcome using coarse grain (CG) forcefields to extend the timescale from the ns – μs range to the μs – ms range. The incorporation of large proteins into CG membrane simulations is non-trivial as CG models alone do a poor job maintaining protein tertiary structure and retaining ion coordination observed in experiments or aMDs. The former was addressed by the application and comparison of the ElNeDyn and GoMARTINI methods of protein restraint. Both methods were refined until key metrics RMSD, RMSF, and principal components were comparable to those observed during aMDs. Further, suitable restraints for Annexin A2-associated calcium ions were derived from atomistic simulations. Here we present a robust coarse-grain model of Annexin A2, suitable for use in the simulation of large biological systems, complete with atomistic-like dynamics and retention of calcium ions.

Generating a coarse-grain annexin A2 model with dynamics comparable to atomistic simulations

ACS Fall 2021

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