Modelling Dynamics in Protein Crystal Structures by Ensemble Refinement
News Jan 28, 2013
Single-structure models derived from X-ray data do not adequately account for the inherent, functionally important dynamics of protein molecules. We generated ensembles of structures by time-averaged refinement, where local molecular vibrations were sampled by molecular-dynamics (MD) simulation whilst global disorder was partitioned into an underlying overall translation–libration–screw (TLS) model. Modeling of 20 protein datasets at 1.1–3.1 Å resolution reduced cross-validated Rfree values by 0.3–4.9%, indicating that ensemble models fit the X-ray data better than single structures. The ensembles revealed that, while most proteins display a well-ordered core, some proteins exhibit a ‘molten core’ likely supporting functionally important dynamics in ligand binding, enzyme activity and protomer assembly. Order–disorder changes in HIV protease indicate a mechanism of entropy compensation for ordering the catalytic residues upon ligand binding by disordering specific core residues. Thus, ensemble refinement extracts dynamical details from the X-ray data that allow a more comprehensive understanding of structure–dynamics–function relationships.
This article was published online in eLife and is free to access.
Biomarker for Glioblastoma Predicts Clinical Course and Sensitivity to TreatmentNews
Scientists validate a biomarker indicative of patients with Glioblastoma prognosis and likely response to specific therapies.READ MORE
Comments | 0 ADD COMMENT
Annual Conference on Antimicrobials and Drug Resistance
Sep 24 - Sep 25, 2018
1st Alpine Winter Conference on Medicinal and Synthetic Chemistry
Jan 28 - Feb 01, 2018