Related Experiment Video
Updated: Jul 3, 2025

Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
Assessment of Two Restraint Potentials for Coarse-Grained Chemical-Cross-Link-Assisted Modeling of Protein Structures
Mateusz Leśniewski1, Maciej Pyrka1,2, Cezary Czaplewski1
1Faculty of Chemistry, University of Gdańsk, Fahrenheit Union of Universities, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland.
Abstract:
The influence of distance restraints from chemical cross-link mass spectroscopy (XL-MS) on the quality of protein structures modeled with the coarse-grained UNRES force field was assessed by using a protocol based on multiplexed replica exchange molecular dynamics, in which both simulated and experimental cross-link restraints were employed, for 23 small proteins. Six cross-links with upper distance boundaries from 4 Å to 12 Å (azido benzoic acid succinimide (ABAS), triazidotriazine (TATA), succinimidyldiazirine (SDA), disuccinimidyl adipate (DSA), disuccinimidyl glutarate (DSG), and disuccinimidyl suberate (BS3)) and two types of restraining potentials ((i) simple flat-bottom Lorentz-like potentials dependent on side chain distance (all cross-links) and (ii) distance- and orientation-dependent potentials determined based on molecular dynamics simulations of model systems (DSA, DSG, BS3, and SDA)) were considered. The Lorentz-like potentials with properly set parameters were found to produce a greater number of higher-quality models compared to unrestrained simulations than the MD-based potentials, because the latter can force too long distances between side chains. Therefore, the flat-bottom Lorentz-like potentials are recommended to represent cross-link restraints. It was also found that significant improvement of model quality upon the introduction of cross-link restraints is obtained when the sum of differences of indices of cross-linked residues exceeds 150.
More Related Videos
14:44Structure and Coordination Determination of Peptide-metal Complexes Using 1D and 2D 1H NMR
Published on: December 16, 2013
10:01Combining Chemical Cross-linking and Mass Spectrometry of Intact Protein Complexes to Study the Architecture of Multi-subunit Protein Assemblies
Published on: November 28, 2017
Related Concept Videos
Ligand Binding and Linkage
Protein-protein Interfaces
Molecular Models
Protein Organization
The primary structure of a protein is its amino acid sequence....
Conserved Binding Sites
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
The Equilibrium Binding Constant and Binding Strength