Change in backbone torsion angle distribution on protein folding

Understanding protein folding requires the determination of the configurati onal space accessible to the protein at different stages in folding. Here, computer simulation analysis of small angle neutron scattering results is u sed to probe the change in the distribution of configurations on strong den aturation of a globular protein, phosphoglycerate kinase, in 4 M guanidine hydrochloride solution. To do this atomic-detail ensembles of the unfolded protein chain are modeled and their scattering profiles compared with the e xperiment. The local conformational statistics are found to strongly influe nce the experimental intensity at scattering vectors between 0.05 and 0.3 A ngstrom(-1). Denaturation leads to a reduction in the protein atom-pair dis tance distribution function over the similar to 3-15 Angstrom region that i s associated with a quantifiable shift in the backbone torsional angle (phi , psi) distribution toward the beta region of the Ramachandran plot.