Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.3.3.1 (
citrate synthase
)
4,488
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Small-angle X-ray and small-angle neutron scattering (SAXS/
SANS
) provide unique structural information on biomolecules and their complexes in solution.
SANS
may provide multiple independent data sets by means of contrast variation experiments, that is, by measuring at different D
2
O concentrations and different perdeuteration conditions of the biomolecular complex. However, even the combined data from multiple SAXS/
SANS
sets is by far insufficient to define all degrees of freedom of a complex, leading to a significant risk of overfitting when refining biomolecular structures against SAXS/
SANS
data. Hence, to control against overfitting, the low-information SAXS/
SANS
data must be complemented by accurate physical models, and, if possible, refined models should be cross-validated against independent data not used during the refinement. We present a method for refining atomic biomolecular structures against multiple sets of SAXS and
SANS
data using all-atom molecular dynamics simulations. Using the protein
citrate synthase
and the protein/RNA complex Sxl-Unr-
msl2
mRNA as test cases, we demonstrate how multiple SAXS and
SANS
sets may be used for refinement and cross-validation, thereby excluding overfitting during refinement. For the Sxl-Unr-
msl2
complex, we find that perdeuteration of the Unr domain leads to a unique, slightly compacted conformation, whereas other perdeuteration conditions lead to similar solution conformations compared to the nondeuterated state. In line with our previous method for predicting SAXS curves,
SANS
curves were predicted with explicit-solvent calculations, taking atomic models for both the hydration layer and the excluded solvent into account, thereby avoiding the use of solvent-related fitting parameters and solvent-reduced neutron scattering lengths. We expect the method to be useful for deriving and validating solution structures of biomolecules and soft-matter complexes, and for critically assessing whether multiple SAXS and
SANS
sets are mutually compatible.
...
PMID:Combined Small-Angle X-ray and Neutron Scattering Restraints in Molecular Dynamics Simulations. 3125 Oct 56
