Incorporation of Prior Phase Information Strengthens Maximum-Likelihood Structure Refinement

Pannu, Navraj S.; Murshudov, Garib N.; Dodson, E.J.; Read, Randy J.

doi:10.1107/s0907444998004119

Cited by 210 publications

(188 citation statements)

References 25 publications

(24 reference statements)

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“…Further rounds of refinement were also carried out with Refmac5. 28,31 Between refinement rounds, coordinates and electron density maps were studied and adjusted where needed with Xfit. 32 Noncrystallographic symmetry (NCS) restraints were applied to the molecules of the asymmetric unit during refinement and removed for the final round.…”

Section: Data Collection and Refinementmentioning

confidence: 99%

“…27 In order to locate the PYR ligand, a difference Fourier map was calculated with the Collaborative Computational Project 4 (CCP4) 28 suite of programs (S Fall , 29 Sigma-A, 30 and Refmac5 31 for rigid body refinement) using the PDB coordinates (1NOU) of the native β-hexosaminidase B. 1 PYR, sugars, SO 4 ions, and water molecules were not included in the initial rigid body refinement and map calculations but were added in subsequent rounds.…”

Section: Data Collection and Refinementmentioning

confidence: 99%

See 1 more Smart Citation

Crystal Structure of β-Hexosaminidase B in Complex with Pyrimethamine, a Potential Pharmacological Chaperone

et al. 2011

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Abstractβ-Hexosaminidases (β-hex) are a group of glycosyl hydrolase isozymes that break down neutral and sialylated glycosphingolipids in the lysosomes, thereby preventing their buildup in neuronal cells. Some mutants of β-hex have decreased folding stability that results in adult-onset forms of lysosomal storage diseases. However, prevention of the harmful accumulation of glycolipids only requires 10% of wild-type activity. Pyrimethamine (PYR) is a potential pharmacological chaperone that works by stabilizing these mutant enzymes sufficiently to allow more β-hex to arrive in the lysosome, where it can carry out its function. An X-ray structure of the complex between human β-hexosaminidase B (HexB) and PYR has been determined to 2.8 Å. PYR binds to the active site of HexB where several favorable van der Waals contacts and hydrogen bonds are † Accession Codes PDB code: 3LMY.

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Section: Data Collection and Refinementmentioning

confidence: 99%

Section: Data Collection and Refinementmentioning

confidence: 99%

Crystal Structure of β-Hexosaminidase B in Complex with Pyrimethamine, a Potential Pharmacological Chaperone

et al. 2011

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“…Re®nements were repeated with three different re®nement targets: least-squares residual (LSQ), maximum likelihood based on amplitudes (MLF; Pannu & Read, 1996) and maximum likelihood incorporating experimental phase informa- tion (MLHL; Pannu et al, 1998). In all cases a¯at bulk-solvent model (Jiang & Brunger, 1994) and overall anisotropic Bfactor correction were applied.…”

Section: Re®nement Protocolsmentioning

confidence: 99%

“…et al, 1997; Pannu et al, 1998). Thus, even single isomorphous replacement (SIR) phases from one heavy-atom derivative can be useful.…”

Section: Introductionmentioning

confidence: 99%

Extending the limits of molecular replacement through combined simulated annealing and maximum-likelihood refinement

Adams¹,

Pannu²,

Read³

et al. 1999

Acta Crystallogr D Biol Cryst

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Phases determined by the molecular-replacement method often suffer from model bias. In extreme cases, the re®nement of the atomic model can stall at high free R values when the resulting electron-density maps provide little indication of how to correct the model, sometimes rendering even a correct solution unusable. Here, it is shown that several recent advances in re®nement methodology allow productive re®ne-ment, even in cases where the molecular-replacement-phased electron-density maps do not allow manual rebuilding. In test calculations performed with a series of homologous models of penicillopepsin using either backbone atoms, or backbone atoms plus conserved core residues, model bias is reduced and re®nement can proceed ef®ciently, even if the initial model is far from the correct one. These new methods combine crossvalidation, torsion-angle dynamics simulated annealing and maximum-likelihood target functions. It is also shown that the free R value is an excellent indicator of model quality after re®nement, potentially discriminating between correct and incorrect molecular-replacement solutions. The use of phase information, even in the form of bimodal single-isomorphousreplacement phase distributions, greatly improves the radius of convergence of re®nement and hence the quality of the electron-density maps, further extending the limits of molecular replacement.

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“…Use of the partial free data concept (Lunin & Skovoroda, 1995) showed that the refinement was successful. As a consequence, ML refinement has been widely adopted by the crystallographic community (Pannu & Read, 1996;Bricogne & Irwin, 1996;Murshudov et al, 1997;Adams et al, 1997;Pannu et al, 1998). Today, the free, model-unbiased fraction of data typically consists of 5% of the diffraction data.…”

Section: Introductionmentioning

confidence: 99%

Free kick instead of cross-validation in maximum-likelihood refinement of macromolecular crystal structures

Pražnikar

Turk

2014

Acta Cryst D Biol Crystallogr

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The refinement of a molecular model is a computational procedure by which the atomic model is fitted to the diffraction data. The commonly used target in the refinement of macromolecular structures is the maximum-likelihood (ML) function, which relies on the assessment of model errors. The current ML functions rely on cross-validation. They utilize phase-error estimates that are calculated from a small fraction of diffraction data, called the test set, that are not used to fit the model. An approach has been developed that uses the work set to calculate the phase-error estimates in the ML refinement from simulating the model errors via the random displacement of atomic coordinates. It is called ML free-kick refinement as it uses the ML formulation of the target function and is based on the idea of freeing the model from the model bias imposed by the chemical energy restraints used in refinement. This approach for the calculation of error estimates is superior to the cross-validation approach: it reduces the phase error and increases the accuracy of molecular models, is more robust, provides clearer maps and may use a smaller portion of data for the test set for the calculation of R free or may leave it out completely.

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Incorporation of Prior Phase Information Strengthens Maximum-Likelihood Structure Refinement

Cited by 210 publications

References 25 publications

Crystal Structure of β-Hexosaminidase B in Complex with Pyrimethamine, a Potential Pharmacological Chaperone

Crystal Structure of β-Hexosaminidase B in Complex with Pyrimethamine, a Potential Pharmacological Chaperone

Extending the limits of molecular replacement through combined simulated annealing and maximum-likelihood refinement

Free kick instead of cross-validation in maximum-likelihood refinement of macromolecular crystal structures

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