Related Experiment Video
Updated: May 29, 2026
10:58
Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
Energy landscape and global optimization for a frustrated model protein
Mark T Oakley1, David J Wales, Roy L Johnston
1School of Chemistry, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
The Journal of Physical Chemistry. B
|August 27, 2011
Summary
Investigating the 69-residue BLN protein reveals a complex energy landscape. This frustrated protein model exhibits multiple deep funnels, each leading to a distinct beta-barrel structure.
Area of Science:
- Computational biology
- Protein folding dynamics
- Biophysics
Background:
- The three-color (BLN) 69-residue model protein was designed to exhibit frustrated folding.
- Frustrated proteins present challenges for understanding folding pathways and identifying the global minimum energy state.
- Gō models simplify protein interactions, reducing landscape frustration for comparative analysis.
Purpose of the Study:
- To investigate the energy landscape of the 69-residue BLN protein.
- To compare the landscape of the frustrated BLN protein with a simplified Gō model.
- To evaluate global optimization techniques for navigating frustrated energy landscapes.
Main Methods:
- Utilizing disconnectivity graphs to map the protein's energy landscape.
- Employing basin-hopping and genetic algorithms to search for the global minimum.
- Comparing the 69-residue BLN protein's landscape to a Gō model and the 46-residue BLN protein.
Main Results:
- The energy landscape of the 69-residue BLN protein is characterized by several deep funnels.
- Each identified funnel corresponds to a unique beta-barrel structure.
- The study provides insights into the performance of global optimization algorithms on frustrated systems.
Conclusions:
- The 69-residue BLN protein's energy landscape supports multiple stable beta-barrel conformations.
- Disconnectivity graphs effectively reveal the complex folding pathways of frustrated proteins.
- Global optimization techniques show promise in navigating challenging energy landscapes for protein design.
Related Concept Videos
02:05Entropy and Solvation
The process of surrounding a solute with solvent is called solvation. It involves evenly distributing the solute within the solvent. The rule of thumb for determining a solvent for a given compound is that like dissolves like. A good solvent has molecular characteristics similar to those of the compound to be dissolved. For example, polar solutions dissolve polar solutes, and apolar solvents dissolve apolar solutes. A polar solvent is a solvent that has a high dielectric constant (ϵ ≥ 15); an...
01:13Induced-fit Model
Most chemical reactions in cells require enzymes—biological catalysts that speed up the reaction without being consumed or permanently changed. They reduce the activation energy needed to convert the reactants into products. Enzymes are proteins, that usually work by binding to a substrate—a reactant molecule that they act upon.
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical characteristics of...
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical characteristics of...
02:00Molecular Models
Physical models representing molecular architectures of chemical compounds play essential roles in understanding chemistry. The use of molecular models makes it easier to visualize the structures and shapes of atoms and molecules.
01:49Conserved Binding Sites
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
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 analyses the...
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 analyses the...
01:29Mechanistic Models: Compartment Models in Algorithms for Numerical Problem Solving
Mechanistic models play a crucial role in algorithms for numerical problem-solving, particularly in nonlinear mixed effects modeling (NMEM). These models aim to minimize specific objective functions by evaluating various parameter estimates, leading to the development of systematic algorithms. In some cases, linearization techniques approximate the model using linear equations.
In individual population analyses, different algorithms are employed, such as Cauchy's method, which uses a...
In individual population analyses, different algorithms are employed, such as Cauchy's method, which uses a...
02:04Protein-Protein Interfaces
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...