Open AccessUsing prime‐and‐switch phasing to reduce model bias in molecular replacement
Author(s) -
Terwilliger Thomas C.
Publication year - 2004
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s0907444904019535
Subject(s) - phaser , electron density , prime (order theory) , resolution (logic) , macromolecule , molecular replacement , set (abstract data type) , yield (engineering) , range (aeronautics) , electron , biological system , statistical physics , computational physics , chemical physics , chemistry , materials science , algorithm , computer science , crystallography , physics , mathematics , thermodynamics , crystal structure , optics , artificial intelligence , quantum mechanics , biochemistry , programming language , combinatorics , biology , composite material
Atomic models are commonly used to calculate phases in macromolecular crystallography. When combined with measured amplitudes, model‐based phases yield electron‐density maps with features of the correct structure but with a significant bias towards features of the model. The present contribution shows applications of the technique of prime‐and‐switch phasing to reduce this bias. An atomic model is used to generate phases that are close to the correct set but that may be biased. An unbiased source of phase information, an estimate of the probability that the electron‐density map corresponds to a macromolecule, is then used to select a set of phases that are near the biased set, without further reference to the biased phases. The probability that the electron‐density map corresponds to a macromolecule is based on agreement of the map with expectations such as a flat solvent region. Prime‐and‐switch phasing can be useful even for crystals with low solvent content and may reduce errors in interpretation of electron density in a wide range of applications of macromolecular crystallography, including molecular replacement, model building, ligand‐binding and conformation‐change studies, refinement and structure validation.