An integrated structural approach reveals novel insights on the BRCA2 - RAD51 interaction

An integrative approach is well suited for the study of highly challenging systems displaying complex conformational dynamics, such as intrinsically disordered proteins like the BRCA2-RAD51 complexes. In this project we would like to couple SAXS, cross-linking mass spectrometry (XL-MS) data, AlphaFold2 predictions, and molecular dynamics (MD) simulations to refine the studies on these complexes. Indeed, SAXS experiments can provide insights into the conformational dynamics in solution, while its limited resolution can be overcome by combining it with MD simulations, which offer an atomistic description. Within this framework, AlphaFold2 predictions can generate initial structural hypotheses for further refinement using combined MD-SAXS when structural models are unavailable. In this context, XL-MS data would provide extremely valuable support, as they can be used to apply constraints in the simulations toward the proper structural ensemble.