Martini bead form factors for nucleic acids and their application in the refinement of protein–nucleic acid complexes against SAXS data

Abstract

The use of small-angle X-ray scattering (SAXS) in combination with molecular dynamics simulation is hampered by its heavy computational cost. The calculation of SAXS from atomic structures can be speeded up by using a coarse-grain representation of the structure. Following the work of Niebling, Bjö rling & Westenhoff [J. Appl. Cryst. (2014), 47, 1190-1198], the Martini bead form factors for nucleic acids have been derived and then implemented, together with those previously determined for proteins, in the publicly available PLUMED library. A hybrid multi-resolution strategy has also been implemented to perform SAXS restrained simulations at atomic resolution by calculating the virtual positions of the Martini beads on the fly and using them for the calculation of SAXS. The accuracy and efficiency of the method are demonstrated by refining the structure of two protein-nucleic acid complexes. Instrumental for this result is the use of metainference, which allows the consideration and alleviation of the approximations at play in the present SAXS calculations. research papers J. Appl. Cryst. (2019). 52, 394-402 Cristina Paissoni et al. Martini bead form factors for nucleic acids 395

Refinement ofα-synuclein ensembles against SAXS data: Comparison of force fields and methods

“…We conducted SAXS-restrained MD simulation using the metainference metadynamics (M&M) method, where we employed the parallel-bias (PBMetaD) flavour of well-tempered metadynamics (Pfaendtner and Bonomi, 2015) in combination with the multiple-walkers scheme (Raiteri et al, 2006). During the M&M simulation, the SAXS back-calculation step utilises a hybrid-resolution approach, where the SAXS data is calculated on-the-fly using 'Martini beads' that are superimposed on the all-atom structures using PLUMED (Bonomi and Camilloni, 2017;Paissoni et al, 2019Paissoni et al, , 2020Jussupow et al, 2020). The approach is particularly efficient as the SAXS back-calculation is calculated using the Debye equation from a coarse-grained model and the excess of electron density in the hydration shell is neglected (Niebling et al, 2014;Paissoni et al, 2020).…”

MARTINI-Based Protein-DNA Coarse-Grained HADDOCKing

“…Despite this difference in sampling, both approaches perform rather similarly in terms of structure quality, indicating that our CG protocol is also applicable for integrative modeling of complexes in combination with real experimental data. Recent studies have indicated that the interpretation of CG models using experimental data, and in particular SAXS data, can benefit from improved forward models as demonstrated by Paissoni et al (2019) for protein-DNA complexes.…”

Data-Driven Molecular Dynamics: A Multifaceted Challenge

“…Finally, SAXS intensities were also explored as a source of experimental information to be used with metainference. Paissoni and coworkers exploited this strategy to investigate the conformational ensemble of K63-linked diubiquitin [148] and to refine models of nucleic acid-protein complexes [149]. Similarly, Kooshapur et al used SAXS experimental data in a metainference framework to derive a structural model of a complex between an RNA-binding protein and a microRNA [150].…”