Complexes++: Efficient and versatile coarse-grained simulations of protein complexes and their dense solutions

The interiors of living cells are densely filled with proteins and their complexes, which perform multitudes of biological functions. We use coarse-grained simulations to reach the system sizes and time scales needed to study protein complexes and their dense solutions, and to interpret experiments. To take full advantage of coarse-graining, the models have to be implemented efficiently in simulation engines that are easy to use, modify, and extend. Here, we introduce the Complexes++ simulation software to simulate a residue-level coarse-grained model for proteins and their complexes [Kim and Hummer, J. Mol. Biol. (2008)], applying a Markov chain Monte Carlo engine to sample configurations. We designed a parallelization scheme for the energy evaluation capable of simulating both dilute and dense systems efficiently. Additionally, we designed the software toolbox pycomplexes to easily set up complex topologies of multi-protein complexes and their solutions, different thermodynamic ensembles, and replica-exchange simulations, to grow flexible polypep- tide structures connecting ordered protein domains, and to automatically visualize structural ensembles. Complexes++ simulations can be easily modified and they can be used for efficient explorations of differ- ent simulation systems and settings. Thus, the Complexes++ software is well suited for the integration of experimental data and for method development.