Less Is More: Coarse-Grained Integrative Modeling of Large Biomolecular Assemblies with HADDOCK

Autor(es)

Roel-Touris, Jorge ^[1] ; Don, Charleen G. ^[2] ; Honorato, Rodrigo V. ^[1] ; Rodrigues, Joao P. G. L. M. ^[3] ; Bonvin, Alexandre M. J. J. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Utrecht, Fac Sci Chem, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht - Netherlands

^[2] Univ Basel, Dept Pharmaceut Sci, CH-4056 Basel - Switzerland

^[3] Stanford Univ, Sch Med, Dept Struct Biol, Stanford, CA 94305 - USA

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CHEMICAL THEORY AND COMPUTATION; v. 15, n. 11, p. 6358-6367, NOV 2019.
• Citações Web of Science: 1

Resumo

Predicting the 3D structure of protein interactions remains a challenge in the field of computational structural biology. This is in part due to difficulties in sampling the complex energy landscape of multiple interacting flexible polypeptide chains. Coarse-graining approaches, which reduce the number of degrees of freedom of the system, help address this limitation by smoothing the energy landscape, allowing an easier identification of the global energy minimum. They also accelerate the calculations, allowing for modeling larger assemblies. Here, we present the implementation of the MARTINI coarse-grained force field for proteins into HADDOCK, our integrative modeling platform. Docking and refinement are performed at the coarse-grained level, and the resulting models are then converted back to atomistic resolution through a distance restraints-guided morphing procedure. Our protocol, tested on the largest complexes of the protein docking benchmark 5, shows an overall similar to 7-fold speed increase compared to standard all-atom calculations, while maintaining a similar accuracy and yielding substantially more near-native solutions. To showcase the potential of our method, we performed simultaneous 7 body docking to model the 1:6 KaiC-KaiB complex, integrating mutagenesis and hydrogen/deuterium exchange data from mass spectrometry with symmetry restraints, and validated the resulting models against a recently published cryo-EM structure. (AU)

• Processo FAPESP: 17/03191-2 - Desenvolvimento e implementação de um modelo de docking Proteína-DNA/RNA do tipo coarse-grained
• Beneficiário: Rodrigo Vargas Honorato
• Modalidade de apoio: Bolsas no Exterior - Pesquisa