Integrating the MARTINI2 Coarse-Grained Force Field into HADDOCK3 for Faster Modelling of Large Biomolecular Complexes

ABSTRACT The integration of coarse-grained (CG) approaches into docking workflows offers a powerful strategy for modelling large biomolecular assemblies with reduced computational costs. We present here the implementation of the MARTINI2 coarse-grained force field into the HADDOCK3 integrative modelling platform. This development enables the use of the CG representations and parameters within HADDOCK3 for efficient sampling and scoring of large protein–protein complexes. The implementation takes advantage of the modular and flexible architecture of HADDOCK3, allowing a seamless combination of MARTINI2 representation with the various modules. Conversion from and to all-atom models is integrated into the coarse-grained modelling workflow. The performance of the protocol is first assessed on protein-protein and protein-DNA benchmarks and then illustrated on a few representative large-scale systems, demonstrating a significant reduction in computational costs while maintaining biologically relevant accuracy.