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

Versini, R.; Reys, V. G. P.; Kravchenko, A.; Honorato, R. V.; Bonvin, A. M. J. J.

2026-04-27 bioinformatics
10.64898/2026.04.25.720800 bioRxiv
Show 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.

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