Method OverviewX-Ray fiber diffraction offers a unique tool to study the molecular organization of fiber-forming macromolecules. For highly oriented fibrillar molecules three-dimensional structures can often be determined from X-ray fiber diffraction data. However, because of limited information content in data structure determination and validation can be challenging.
Our method automatically determines structures of fibrils by guiding Rosetta macromolecular modeling software simulations by fiber diffraction data. By incorporating fiber diffraction data into Rosetta, we increase the radius of convergence, raise data-to-parameter ratio and reduce overfitting to experimental data. We further minimize the risk of overfitting by developing a new cross-validation method that can be easily employed in the modeling framework. Additional restraints from other experiments can also be simultaneously used in structure building and refinement.
In case of questions or problems please contact us at: Wojciech.Potrzebowski@biochemistry.lu.se