Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
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]
Total Authors: 5
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF CHEMICAL THEORY AND COMPUTATION; v. 15, n. 11, p. 6358-6367, NOV 2019.
Web of Science Citations: 1
Abstract

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)

FAPESP's process: 17/03191-2 - Development and implementation of a coarse-grained Protein-DNA/RNA docking model
Grantee:Rodrigo Vargas Honorato
Support Opportunities: Scholarships abroad - Research