Use of TLS parameters to model anisotropic displacements in macromolecular refinement.

By Winn, M. Isupov, G. Murshudov. 2001

1,725 citations recorded by the source corpus.

An essential step in macromolecular refinement is the selection of model parameters which give as good a description of the experimental data as possible while retaining a realistic data-to-parameter ratio. This is particularly true of the choice of atomic displacement parameters, where the move from individual isotropic to individual anisotropic refinement involves a sixfold increase in the number of required displacement parameters. The number of refinement parameters can be reduced by using collective variables rather than independent atomic variables and one of the simplest examples of this is the TLS parameterization for describing the translation, libration and screw-rotation displacements of a pseudo-rigid body. This article describes the implementation of the TLS parameterization in the macromolecular refinement program REFMAC. Derivatives of the residual with respect to the TLS parameters are expanded in terms of the derivatives with respect to individual anisotropic U values, which in turn are calculated using a fast Fourier transform technique. TLS refinement is therefore fast and can be used routinely. Examples of TLS refinement are given for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and a transcription activator GerE, for both of which there is data to only 2.0 A, so that individual anisotropic refinement is not feasible. GAPDH has been refined with between one and four TLS groups in the asymmetric unit and GerE with six TLS groups. In both cases, inclusion of TLS parameters gives improved refinement statistics and in particular an improvement in R and free R values of several percent. Furthermore, GAPDH and GerE have two and six molecules in the asymmetric unit, respectively, and in each case the displacement parameters differ significantly between molecules. These differences are well accounted for by the TLS parameterization, leaving residual local displacements which are very similar between molecules and to which NCS restraints can be applied.

Subfields: Materials Chemistry, Molecular Biology

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Citations in the corpus

Towards automated crystallographic structure refinement with phenix.refine (2012, methodology): “Finally, small (in the harmonic approximation) local atomic vibrations, Ulocal, can be modeled using a less detailed isotropic model that uses only one parameter per atom or using a more detailed (and accurate) anisotropic parameterization that includes six parameters per atom and therefore requires”
Overview of the CCP4 suite and current developments (2011, methodology): “REFMAC5 will refine atomic coordinates and atomic isotropic or anisotropic displacement parameters (Murshudov et al., 1999), as well as group parameters for rigid-body refinement and TLS refinement (Winn et al., 2001, 2003).”
A series of PDB-related databanks for everyday needs (2014, background): “Residual B-factors do not include the contribution of the TLS motion (29).”
From deep TLS validation to ensembles of atomic models built from elemental motions. II. Analysis of TLS refinement results by explicit interpretation (2018, background): “As discussed in the literature (see, for example, Dunitz & White, 1973; Murshudov et al., 1999; Winn et al., 2001), the atomic displacement is a superposition of various motions that arise from different sources.”
Crystal structure of a Rad51 filament (2004, methodology): “The final steps of refinement were carried out with the CCP4 package, using REFMAC5 to apply TLS parameters to the protei”
Structural basis for RNA translocation by DEAH-box ATPases (2019, methodology): “Both structures were refined using the RecA1, RecA2 and Cterminal domains as translation, libration and screw-axis (TLS) groups and with the inclusion of automatically generated local non-crystallographic symmetry (NCS) restraints (41).”
Structural basis for inhibition of the epidermal growth factor receptor by cetuximab. (2005, methodology): “This sEGFR was further purified by size ployed TLS refinement (Winn et al., 2001) with anisotropic motion tensors exclusion chromatography (SEC) using a SEC250 column (BioRad) prerefined for each of the four domains of sEGFR and each domain of equilibrated with 25 mM HEPES, 100 mM NaCl (pH 7.5).”
The Phenix Software for Automated Determination of Macromolecular Structures (2011, methodology): “As the data to parameter ratio approaches unity or worse, it is necessary to apply other constraints, such as refinement of coordinates in torsion angle space[46], or refinement of atomic displacements as constrained rigid groups with the translation-libration-screw (TLS) formulism[54, 55].”
Structure of N-terminal Domain of NPC1 Reveals Distinct Subdomains for Binding and Transfer of Cholesterol (2009, methodology): “, 1998), and the final cycles of refinement were performed with REFMAC (Winn et al., 2001).”
Structures of bovine, equine and leporine serum albumin. (2012, methodology): “In all cases, structure refinement was carried out in REFMAC5 (Murshudov et al., 2011) using maximum-likelihood targets including TLS parameters (Winn et al., 2001) defined for each subdomain and separately for both polypeptide chains in the BSA structure.”
Mechanism of activation and inhibition of the HER4/ErbB4 kinase. (2008, methodology): “TLS groups were generated by TLSMD and used for refinement in REFMAC (Winn et al., 2001).”
Modelling dynamics in protein crystal structures by ensemble refinement (2012, neutral): “Using one TLS group per protein molecule or domain, we iteratively fitted TLS parameters ( Schomaker and Trueblood, 1968 ; Winn et al., 2001 ) to the atomic B -factors of the protein atoms excluding atoms with large deviations in B -factor from the Table 1.”
Crystal structure of a membrane-bound metalloenzyme that catalyses the biological oxidation of methane (2005, background): “Translation liberation screw-rotation (TLS) parameters and restrained refinement options in REFMAC”