Ab Initio Solution of Macromolecular Crystal Structures Without Direct Methods
Ab initio solution of macromolecular crystal structures without direct methods Airlie J. McCoya, Robert D. Oeffnera, Antoni G. Wrobelb, Juha R. M. Ojalac, Karl Tryggvasonc,d, Bernhard Lohkampe, and Randy J. Reada,1 aDepartment of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom; bDepartment of Clinical Biochemistry, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom; cDivision of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden; dCardiovascular and Metabolic Disorders Program, Duke-NUS (National University of Singapore) Medical School, 16957 Singapore; and eDivision of Molecular Structural Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden Edited by Axel T. Brunger, Stanford University, Stanford, CA, and approved February 27, 2017 (received for review January 30, 2017) The majority of macromolecular crystal structures are determined (optionally) a correction for the effect of disordered solvent using the method of molecular replacement, in which known described by the parameters fsol and Bsol: related structures are rotated and translated to provide an initial sffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi atomic model for the new structure. A theoretical understanding 2 2 Bsol 2π Δ of the signal-to-noise ratio in likelihood-based molecular replace- σA = fP 1 − fsolexp − exp − , [1a] d2 d2 ment searches has been developed to account for the influence of 4 3 model quality and completeness, as well as the resolution of the diffraction data. Here we show that, contrary to current belief, pffiffiffiffi 2π2 Δ2 molecular replacement need not be restricted to the use of models σA ≈ fPexp − .
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