Overall Summary/Abstract The Phenix software has been developed as a result of the highly collaborative work of 4 groups located at Lawrence Berkeley Laboratory, Los Alamos National Laboratory, Cambridge University, and Duke University. Building on our prior work we will continue to collaborate in the development of new methods to improve structure solution, with a focus on low (near atomic) resolution (3-4.5). Researchers still encounter significant problems in solving and completing structures in this regime. Improvements in single wavelength anomalous (SAD) phasing, molecular replacement, model building, refinement and validation will make it possible for researchers to tackle more challenging experimental systems. This is particularly timely as new approaches to data collection, such as serial crystallography, are producing lower resolution structures of membrane proteins and large flexible complexes. Recent developments in the field of single particle cryo-electron microscopy (cryo-EM) have generated a rapid growth in the number of large macromolecular complexes solved ab initio. Therefore, a significant area of development for the Phenix team in the next 5 years will be cryo-EM, in particular near atomic resolution single particle image reconstruction. This is one of the most exciting developments in the field of structural biology in recent history. Our goal will be to collaborate to extend our current methods, and develop new ones, to address the problems of model fitting, model building, refinement and validation of atomic models derived from cryo-EM maps.