Accurate Protein Dynamic Conformational Ensembles: Combining AlphaFold, MD and Amide15N(1H) NMR Relaxation

Abstract Conformational heterogeneity is critical for protein function, but the validation of dynamic ensembles remains a challenge. In this study, we introduced an approach that integrates free MD simulations, using an AlphaFold-generated structure as the starting point, with experimental relaxation data to identify biologically relevant conformational ensembles. For the extracellular region of Streptococcus pneumoniae PsrSp, we found that only certain segments of the MD long trajectory aligned well with experimental data. The defined ensembles revealed two regions with increased flexibility that play important functional roles. Competing Interest Statement The authors have declared no competing interest. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.