Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fitting molecular fragments into electron density.

ABSTRACT: Molecular replacement is a powerful tool for the location of large models using structure-factor magnitudes alone. When phase information is available, it becomes possible to locate smaller fragments of the structure ranging in size from a few atoms to a single domain. The calculation is demanding, requiring a six-dimensional rotation and translation search. A number of approaches have been developed to this problem and a selection of these are reviewed in this paper. The application of one of these techniques to the problem of automated model building is explored in more detail, with particular reference to the problem of sequencing a protein main-chain trace.

SUBMITTER: Cowtan K

PROVIDER: S-EPMC2394793 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Fitting molecular fragments into electron density.

Cowtan Kevin K

Acta crystallographica. Section D, Biological crystallography 20071205 Pt 1

Molecular replacement is a powerful tool for the location of large models using structure-factor magnitudes alone. When phase information is available, it becomes possible to locate smaller fragments of the structure ranging in size from a few atoms to a single domain. The calculation is demanding, requiring a six-dimensional rotation and translation search. A number of approaches have been developed to this problem and a selection of these are reviewed in this paper. The application of one of t ...[more]

PMID: 18094471

Similar Datasets

Determining macromolecular assembly structures by molecular docking and fitting into an electron density map.

Project description:Structural models of macromolecular assemblies are instrumental for gaining a mechanistic understanding of cellular processes. Determining these structures is a major challenge for experimental techniques, such as X-ray crystallography, NMR spectroscopy and electron microscopy (EM). Thus, computational modeling techniques, including molecular docking, are required. The development of most molecular docking methods has so far been focused on modeling of binary complexes. We have recently introduced the MultiFit method for modeling the structure of a multisubunit complex by simultaneously optimizing the fit of the model into an EM density map of the entire complex and the shape complementarity between interacting subunits. Here, we report algorithmic advances of the MultiFit method that result in an efficient and accurate assembly of the input subunits into their density map. The successful predictions and the increasing number of complexes being characterized by EM suggests that the CAPRI challenge could be extended to include docking-based modeling of macromolecular assemblies guided by EM.

| S-EPMC2952722 | biostudies-literature

Fitting high-resolution electron density maps from atomic models to solution scattering data.

Project description:Solution scattering techniques, such as small and wide-angle X-ray scattering (SWAXS), provide valuable insights into the structure and dynamics of biological macromolecules in solution. In this study, we present an approach to accurately predict solution X-ray scattering profiles at wide angles from atomic models by generating high-resolution electron density maps. Our method accounts for the excluded volume of bulk solvent by calculating unique adjusted atomic volumes directly from the atomic coordinates. This approach eliminates the need for a free fitting parameter commonly used in existing algorithms, resulting in improved accuracy of the calculated SWAXS profile. An implicit model of the hydration shell is generated which uses the form factor of water. Two parameters, namely the bulk solvent density and the mean hydration shell contrast, are adjusted to best fit the data. Results using eight publicly available SWAXS profiles show high quality fits to the data. In each case, the optimized parameter values show small adjustments demonstrating that the default values are close to the true solution. Disabling parameter optimization results in a significant improvement of the calculated scattering profiles compared to the leading software. The algorithm is computationally efficient, showing more than tenfold reduction in execution time compared to the leading software. The algorithm is encoded in a command line script called denss.pdb2mrc.py and is available open source as part of the DENSS v1.7.0 software package (https://github.com/tdgrant1/denss). In addition to improving the ability to compare atomic models to experimental SWAXS data, these developments pave the way for increasing the accuracy of modeling algorithms utilizing SWAXS data while decreasing the risk of overfitting.

| S-EPMC10312546 | biostudies-literature

TEMPy2: a Python library with improved 3D electron microscopy density-fitting and validation workflows.

Project description:Structural determination of molecular complexes by cryo-EM requires large, often complex processing of the image data that are initially obtained. Here, TEMPy2, an update of the TEMPy package to process, optimize and assess cryo-EM maps and the structures fitted to them, is described. New optimization routines, comprehensive automated checks and workflows to perform these tasks are described.

| S-EPMC7787107 | biostudies-literature

Cryo-electron microscopy modeling by the molecular dynamics flexible fitting method.

Project description:The increasing power and popularity of cryo-electron microscopy (cryo-EM) in structural biology brought about the development of so-called hybrid methods, which permit the interpretation of cryo-EM density maps beyond their nominal resolution in terms of atomic models. The Cryo-EM Modeling Challenge 2010 is the first community effort to bring together developers of hybrid methods as well as cryo-EM experimentalists. Participating in the challenge, the molecular dynamics flexible fitting (MDFF) method was applied to a number of cryo-EM density maps. The results are described here with special emphasis on the use of symmetry-based restraints to improve the quality of atomic models derived from density maps of symmetric complexes; on a comparison of the stereochemical quality of atomic models resulting from different hybrid methods; and on application of MDFF to electron crystallography data.

| S-EPMC3376020 | biostudies-literature

MultiFit: a web server for fitting multiple protein structures into their electron microscopy density map.

Project description:Advances in electron microscopy (EM) allow for structure determination of large biological assemblies at increasingly higher resolutions. A key step in this process is fitting multiple component structures into an EM-derived density map of their assembly. Here, we describe a web server for this task. The server takes as input a set of protein structures in the PDB format and an EM density map in the MRC format. The output is an ensemble of models ranked by their quality of fit to the density map. The models can be viewed online or downloaded from the website. The service is available at; http://salilab.org/multifit/ and http://bioinfo3d.cs.tau.ac.il/.

| S-EPMC3125811 | biostudies-literature

Flexible fitting of atomic structures into electron microscopy maps using molecular dynamics.

Project description:A novel method to flexibly fit atomic structures into electron microscopy (EM) maps using molecular dynamics simulations is presented. The simulations incorporate the EM data as an external potential added to the molecular dynamics force field, allowing all internal features present in the EM map to be used in the fitting process, while the model remains fully flexible and stereochemically correct. The molecular dynamics flexible fitting (MDFF) method is validated for available crystal structures of protein and RNA in different conformations; measures to assess and monitor the fitting process are introduced. The MDFF method is then used to obtain high-resolution structures of the E. coli ribosome in different functional states imaged by cryo-EM.

| S-EPMC2430731 | biostudies-literature

Normal mode-based fitting of atomic structure into electron density maps: application to sarcoplasmic reticulum Ca-ATPase.

Project description:A method for the flexible docking of high-resolution atomic structures into lower resolution densities derived from electron microscopy is presented. The atomic structure is deformed by an iterative process using combinations of normal modes to obtain the best fit of the electron microscopical density. The quality of the computed structures has been evaluated by several techniques borrowed from crystallography. Two atomic structures of the SERCA1 Ca-ATPase corresponding to different conformations were used as a starting point to fit the electron density corresponding to a different conformation. The fitted models have been compared to published models obtained by rigid domain docking, and their relation to the known crystallographic structures are explored by normal mode analysis. We find that only a few number of modes contribute significantly to the transition. The associated motions involve almost exclusively rotation and translation of the cytoplasmic domains as well as displacement of cytoplasmic loops. We suggest that the movements of the cytoplasmic domains are driven by the conformational change that occurs between nonphosphorylated and phosphorylated intermediate, the latter being mimicked by the presence of vanadate at the phosphorylation site in the electron microscopy structure.

| S-EPMC1305158 | biostudies-literature

Automated ligand fitting by core-fragment fitting and extension into density.

Project description:A procedure for fitting of ligands to electron-density maps by first fitting a core fragment of the ligand to density and then extending the remainder of the ligand into density is presented. The approach was tested by fitting 9327 ligands over a wide range of resolutions (most are in the range 0.8-4.8 A) from the Protein Data Bank (PDB) into (Fo - Fc)exp(i phi(c)) difference density calculated using entries from the PDB without these ligands. The procedure was able to place 58% of these 9327 ligands within 2 A (r.m.s.d.) of the coordinates of the atoms in the original PDB entry for that ligand. The success of the fitting procedure was relatively insensitive to the size of the ligand in the range 10-100 non-H atoms and was only moderately sensitive to resolution, with the percentage of ligands placed near the coordinates of the original PDB entry for fits in the range 58-73% over all resolution ranges tested.

| S-EPMC2745883 | biostudies-literature

Targeted conformational search with map-restrained self-guided Langevin dynamics: application to flexible fitting into electron microscopic density maps.

Project description:We present a map-restrained self-guided Langevin dynamics (MapSGLD) simulation method for efficient targeted conformational search. The targeted conformational search represents simulations under restraints defined by experimental observations and/or by user specified structural requirements. Through map-restraints, this method provides an efficient way to maintain substructures and to set structure targets during conformational searching. With an enhanced conformational searching ability of self-guided Langevin dynamics, this approach is suitable for simulating large-scale conformational changes, such as the formation of macromolecular assemblies and transitions between different conformational states. Using several examples, we illustrate the application of this method in flexible fitting of atomic structures into density maps derived from cryo-electron microscopy.

| S-EPMC3785014 | biostudies-literature

Molecular surface mesh generation by filtering electron density map.

Project description:Bioinformatics applied to macromolecules are now widely spread and in continuous expansion. In this context, representing external molecular surface such as the Van der Waals Surface or the Solvent Excluded Surface can be useful for several applications. We propose a fast and parameterizable algorithm giving good visual quality meshes representing molecular surfaces. It is obtained by isosurfacing a filtered electron density map. The density map is the result of the maximum of Gaussian functions placed around atom centers. This map is filtered by an ideal low-pass filter applied on the Fourier Transform of the density map. Applying the marching cubes algorithm on the inverse transform provides a mesh representation of the molecular surface.

| S-EPMC2856016 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data