Structure refinement of protein model decoys requires accurate side-chain placement

2012 ◽  
Vol 81 (3) ◽  
pp. 469-478 ◽  
Author(s):  
Mark A. Olson ◽  
Michael S. Lee
Keyword(s):  
Structure Refinement ◽  
Side Chain ◽  
Protein Model

scholarly journals CLP-based protein fragment assembly

2010 ◽  
Vol 10 (4-6) ◽  
pp. 709-724 ◽  
Author(s):  
ALESSANDRO DAL PALÙ ◽  
AGOSTINO DOVIER ◽  
FEDERICO FOGOLARI ◽  
ENRICO PONTELLI
Keyword(s):  
Search Strategy ◽  
Protein Structures ◽  
Constraint Solving ◽  
Side Chain ◽  
Space Filling ◽  
Protein Fragment ◽  
Fragment Assembly ◽  
Energy Models ◽  
Novel Approach ◽  
Protein Model

AbstractThe paper investigates a novel approach, based on Constraint Logic Programming (CLP), to predict the 3D conformation of a protein via fragments assembly. The fragments are extracted by a preprocessor—also developed for this work—from a database of known protein structures that clusters and classifies the fragments according to similarity and frequency. The problem of assembling fragments into a complete conformation is mapped to a constraint solving problem and solved using CLP. The constraint-based model uses a medium discretization degree Cα-side chain centroid protein model that offers efficiency and a good approximation for space filling. The approach and adapts existing energy models to the protein representation used and applies a large neighboring search strategy. The results shows the feasibility and efficiency of the method. The declarative nature of the solution allows to include future extensions, e.g., different size fragments for better accuracy.

scholarly journals When good ligands go bad

2014 ◽  
Vol 70 (a1) ◽  
pp. C1269-C1269
Author(s):  
Ethan Merritt
Keyword(s):  
Task Force ◽  
Structure Refinement ◽  
Binding Pocket ◽  
Software Packages ◽  
Protein Model ◽  
Protein Components ◽  
First Time ◽  
Standard Software ◽  
New Protein

"Tools for validating structural models of proteins are relatively mature and widely implemented. New protein crystallographers are introduced early on to the importance of monitoring conformance with expected φ/ψ values, favored rotamers, and local stereochemistry. The protein model is validated by the PDB at the time of deposition using criteria that are also available in the standard software packages used to refine the model being deposited. By contrast, crystallographers are typically much less familiar with procedures to validate key non-protein components of the model – cofactors, substrates, inhibitors, etc. It has been estimated that as many as a third of all ligands in the PDB exhibit preventable errors of some sort, ranging from minor deviations in expected bond angles to wholly implausible placement in the binding pocket. Following recommendations from the wwPDB Validation Task Force, the PDB recently began validating ligand geometry as an integral part of deposition processing. This means that many crystallographers will soon receive for the first time a ""grade"" on the quality of ligands in the structure they have just deposited. Some will be surprised, as I was following my first PDB deposition of 2014, at how easily bad ligand geometry can slip through the cracks in supposedly robust structure refinement protocols that their lab has used for many years. I will illustrate use of current tools for generating ligand restraints to guide model refinement. One is the jligand+coot+cprodrg pipeline integrated into the CCP4 suite. Another is the Grade web server provided as a community resource by Global Phasing Ltd. Furthermore I will show examples from recent in-house refinements of how things can still go wrong even if you do use these tools, and how we recovered. The new PDB deposition checks may expose errors in your ligand descriptions after the fact. This presentation may help you avoid introducing those errors in the first place."

scholarly journals GalaxyRefine: protein structure refinement driven by side-chain repacking

2013 ◽  
Vol 41 (W1) ◽  
pp. W384-W388 ◽  
Author(s):  
Lim Heo ◽  
Hahnbeom Park ◽  
Chaok Seok
Keyword(s):  
Protein Structure ◽  
Structure Refinement ◽  
Side Chain ◽  
Protein Structure Refinement

scholarly journals Iron–sulfur clusters have no right angles

2019 ◽  
Vol 75 (1) ◽  
pp. 16-20 ◽  
Author(s):  
Nigel W. Moriarty ◽  
Paul D. Adams
Keyword(s):  
High Resolution ◽  
Protein Data Bank ◽  
Structure Refinement ◽  
Data Bank ◽  
Side Chain ◽  
Crystallographic Structure ◽  
Computational Tools ◽  
Iron Sulfur Clusters ◽  
Iron Sulfur ◽  
Structural Database

Accurate geometric restraints are vital in the automation of macromolecular crystallographic structure refinement. A set of restraints for the Fe4S4 cubane-type cluster was created using the Cambridge Structural Database (CSD) and high-resolution structures from the Protein Data Bank. Geometries from each source were compared and pairs of refinements were performed to validate these new restraints. In addition to the restraints internal to the cluster, the CSD was mined to generate bond and angle restraints to be applied to the most common linking motif for Fe4S4: coordination of the four Fe atoms to the side-chain sulfurs of four cysteine residues. Furthermore, computational tools were developed to assist researchers when refining Fe4S4-containing proteins.

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