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Synergy among phase‐refinement techniques in macromolecular crystallography
Author(s) -
Burla Maria Cristina,
Cascarano Giovanni Luca,
Giacovazzo Carmelo,
Polidori Giampiero
Publication year - 2017
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.374
H-Index - 138
ISSN - 2059-7983
DOI - 10.1107/s2059798317014590
Subject(s) - phase (matter) , crystallography , macromolecule , materials science , chemistry , computer science , computational biology , biology , biochemistry , organic chemistry
Ab initio and non‐ ab initio phasing methods are often unable to provide phases of sufficient quality to allow the molecular interpretation of the resulting electron‐density maps. Phase extension and refinement is therefore a necessary step: its success or failure can make the difference between solution and nonsolution of the crystal structure. Today phase refinement is trusted to electron‐density modification (EDM) techniques, and in practice to dual‐space methods which try, via suitable constraints in direct and in reciprocal space, to generate higher quality electron‐density maps. The most popular EDM approaches, denoted here as mainstream methods, are usually part of packages which assist crystallographers in all of the structure‐solution steps from initial phasing to the point where the molecular model perfectly fits the known features of protein chemistry. Other phase‐refinement approaches that are based on different sources of information, denoted here as out‐of‐mainstream methods, are not frequently employed. This paper aims to show that mainstream and out‐of‐mainstream methods may be combined and may lead to dramatic advances in the present state of the art. The statement is confirmed by experimental tests using molecular‐replacement, SAD–MAD and ab initio techniques.