Pathways for conformational change in nitrogen regulatory protein C from discrete path sampling
1University Chemical Laboratories, Lensfield Road, Cambridge CB2 1EW, UK.
The Journal of Physical Chemistry. B
|February 6, 2008
Summary
Computational methods reveal key pathways for nitrogen regulatory protein C conformational changes. These findings align with experimental data and predict large-scale molecular motion mechanisms.
Area of Science:
- Computational biophysics
- Molecular dynamics
- Protein conformational changes
Background:
- Nitrogen regulatory protein C (NtrC) undergoes significant conformational changes crucial for its function.
- Understanding these large-scale motions is essential for deciphering protein regulation and activity.
Purpose of the Study:
- To computationally determine the pathways involved in the conformational change of nitrogen regulatory protein C (NtrC).
- To identify key structural features of these pathways and compare them with experimental observations.
Main Methods:
- Utilizing the CHARMM19 force field and an implicit solvation model for molecular simulations.
- Employing the discrete path sampling approach to map the potential energy surface.
- Generating a database of local minima and transition states to identify kinetically relevant pathways.
Main Results:
- Calculated conformational change pathways for NtrC.
- Identified pathways contributing significantly to two-state rate constants.
- Observed structural features in calculated pathways that are consistent with experimental findings.
Conclusions:
- The discrete path sampling method successfully identified kinetically relevant pathways for NtrC conformational change.
- The computational results provide valuable insights and predictions for the large-scale motion mechanisms of NtrC.
- Further analysis of these pathways can enhance our understanding of protein function and regulation.
Related Concept Videos
00:52¹H NMR of Conformationally Flexible Molecules: Temporal Resolution
At room temperature, the chair conformer of cyclohexane undergoes rapid ring flipping between two equivalent chair conformers at a rate of approximately 105 times per second. These two chair conformers are in equilibrium. The rapid ring flipping results in the interconversion of the axial proton to an equatorial proton and an equatorial to the axial proton. Such interconversions are too rapid and cannot be detected on the NMR timescale. Hence, the NMR spectrometer cannot distinguish between the...
01:25Protein Folding
Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
01:26Bacterial Protein Maturation
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
01:15¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR
The axial and equatorial protons in cyclohexane can be distinguished by performing a variable-temperature NMR experiment. In this process, except for one proton, the remaining eleven protons are replaced by deuterium. The deuterium substitution avoids the possible peak splitting caused by the spin-spin coupling between the adjacent protons. The remaining proton flips between the axial and equatorial positions.
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.