  Ongoing advances in force field and computer hardware development enable the
use of molecular dynamics (MD) to simulate increasingly complex systems with
the ultimate goal of reaching cellular complexity. At the same time, rational
design by high-throughput (HT) simulations is another forefront of MD. In these
areas, the Martini coarse-grained force field, especially the latest version
(i.e. v3), is being actively explored because it offers enhanced
spatial-temporal resolution. However, the automation tools for preparing
simulations with the Martini force field, accompanying the previous version,
were not designed for HT simulations or studies of complex cellular systems.
Therefore, they become a major limiting factor. To address these shortcomings,
we present the open-source vermouth python library. Vermouth is designed to
become the unified framework for developing programs, which prepare, run, and
analyze Martini simulations of complex systems. To demonstrate the power of the
vermouth library, the martinize2 program is showcased as a generalization of
the martinize script, originally aimed to set up simulations of proteins. In
contrast to the previous version, martinize2 automatically handles protonation
states in proteins and post-translation modifications, offers more options to
fine-tune structural biases such as the elastic network, and can convert
non-protein molecules such as ligands. Finally, martinize2 is used in two
high-complexity benchmarks. The entire I-TASSER protein template database as
well as a subset of 200,000 structures from the AlphaFold Protein Structure
Database are converted to CG resolution and we illustrate how the checks on
input structure quality can safeguard HT applications.
