New Tools and Data for Improving Structures, Using All-Atom Contacts

Abstract

Publisher Summary This chapter reviews new techniques to make significant improvements in the accuracy and reliability of protein and nucleic acid crystal structures. Three major circumstances are responsible for motivating to update the traditional geometric criteria for protein structure validation: (1) the development of the all-atom contact method that can discriminate one major category of physically impossible from possible conformations, (2) the need to omit high B-factor examples that surprisingly has seldom been done before, and (3) the greatly expanded number of structures now available at high resolution. The all-atom contact technique depends on adding the hydrogen atoms, most of which are completely determined to a suitable accuracy by the positions of the heavier atoms. The methodology of macromolecular crystallography is mature, powerful, and effective, and it has transformed the understanding of biology at the molecular level. Macromolecular structures are improved significantly (i.e., made more accurate for a given resolution and data quality) by the use of validation tools, such as the free R factor and Ramachandran plot criteria. A detailed and critical analysis of the contacts and geometry inside macromolecules shows that the structures are remarkably relaxed and, at the same time, remarkably well packed.