Related Experiment Video
Updated: Apr 10, 2026
09:51
Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web
Published on: July 16, 2017
16.2K
cNMA: a framework of encounter complex-based normal mode analysis to model conformational changes in protein
1Toyota Technological Institute at Chicago, Chicago, IL 60637, USA and Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843, USA.
Bioinformatics (Oxford, England)
|June 15, 2015
Summary
We developed a new computational framework, encounter complex-based normal mode analysis (cNMA), to better predict protein conformational changes during interactions. cNMA improves upon existing methods by considering both intrinsic protein flexibility and intermolecular forces for more accurate protein docking.
Area of Science:
- Computational Biology
- Structural Biology
- Biophysics
Background:
- Predicting protein conformational changes during association is a fundamental challenge.
- Conventional normal mode analysis (NMA) using anisotropic network models (ANM) explains protein interactions via conformational selection.
- However, conformational selection alone is insufficient for cases with significant conformational changes, necessitating improved models.
Purpose of the Study:
- To develop a computational framework that improves the prediction of protein conformational changes during interactions.
- To enhance the accuracy and efficiency of protein docking, particularly for cases involving substantial conformational shifts.
- To integrate both intrinsic protein flexibility and intermolecular interactions into a unified analysis.
Main Methods:
- Extended ANM to incorporate concurrent, differentiated intra- and inter-molecular interactions.
- Developed a novel encounter complex-based NMA (cNMA) framework.
- Validated cNMA using theoretical analysis and empirical data from a large dataset of significant conformational changes.
Main Results:
- cNMA generates conformational vectors that better approximate conformational changes than conventional NMA.
- cNMA effectively captures contributions from both intrinsic flexibility and intermolecular interactions.
- Induced motions in both binding partners and their coupling significantly improve prediction accuracy.
- Differentiating intra- and inter-molecular interactions is crucial for accurate modeling.
Conclusions:
- cNMA provides a more accurate approach to modeling protein-protein interactions and conformational dynamics.
- The framework offers improved dimensionality reduction for flexible protein docking.
- Results offer new insights into the molecular mechanisms governing protein associations.
Related Concept Videos
00:52¹H NMR of Conformationally Flexible Molecules: Temporal Resolution
1.4K
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...
1.4K
01:57Protein Complexes with Interchangeable Parts
2.2K
2.2K
01:57Protein Complexes with Interchangeable Parts
3.1K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
3.1K
02:26Protein Networks
4.7K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.7K
02:06Newman Projections
24.5K
Different notations are used to represent the three-dimensional structure of molecules on two-dimensional surfaces. One of the most commonly used representations is the dash-wedge formula. The dashed wedges, solid wedges, and the plane lines indicate the groups situated behind the plane, coming out of the plane, and in the plane, respectively.
The organic molecules rotate across the single bonds leading to numerous temporary three-dimensional structures of varying energy known as...
The organic molecules rotate across the single bonds leading to numerous temporary three-dimensional structures of varying energy known as...
24.5K
01:15¹H NMR of Conformationally Flexible Molecules: Variable-Temperature NMR
1.8K
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.
1.8K