Related Experiment Video
Updated: Aug 14, 2026
05:56
Exploring Caspase Mutations and Post-Translational Modification by Molecular Modeling Approaches
Published on: October 13, 2022
Comment on 'Valid molecular dynamics simulations of human hemoglobin require a surprisingly large box size'
Vytautas Gapsys1, Bert L de Groot1
1Computational Biomolecular Dynamics Group, Max-Planck Institute for Biophysical Chemistry, Göttingen, Germany.
Elife
|June 21, 2019
Summary
A recent study suggested large solvent boxes stabilize hemoglobin. However, our research found this box size dependence is not reproducible and has no significant effect on hemoglobin
Area of Science:
- Biophysics
- Computational Biology
- Protein Dynamics
Background:
- A recent molecular dynamics study suggested that the size of the solvent box significantly impacts hemoglobin stability.
- Specifically, it was proposed that larger solvent boxes are required to stabilize the unliganded T state of hemoglobin.
Purpose of the Study:
- To critically evaluate the findings of El Hage et al. (2018) regarding solvent box size dependence in molecular dynamics simulations of hemoglobin.
- To investigate the reproducibility of the reported box size effects on hemoglobin stability, kinetics, and thermodynamics.
Main Methods:
- Molecular dynamics simulations of hemoglobin.
- Analysis of conformational transitions, kinetics, and thermodynamics.
- Re-evaluation of simulation parameters, specifically solvent box size.
- Increased statistical sampling compared to previous studies.
Main Results:
- The reported dependence of hemoglobin stability on solvent box size was not reproducible with increased statistical sampling.
- No significant effects of solvent box size on the kinetics or thermodynamics of hemoglobin conformational transitions were observed.
- Concerns were raised regarding the methodology and conclusions of the original study.
Conclusions:
- The stability of unliganded hemoglobin in molecular dynamics simulations is not critically dependent on the solvent box size.
- The findings of El Hage et al. (2018) regarding box size effects are questionable.
- Standard simulation parameters are likely sufficient for studying hemoglobin conformational dynamics.
Related Concept Videos
01:18Molecular Shapes
Molecules have characteristic shapes that are crucial for their function. The arrangement of various electron groups around the central atom dictates their molecular geometry. Electron pairs in the valence shell of a central atom will adopt an arrangement that minimizes repulsions between the electron pairs by maximizing the distance between them. The valence electrons form either bonding pairs, located primarily between bonded atoms, or lone pairs.Two regions of electron density in a diatomic...
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.
02:15Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...
02:21Globular and Fibrous Proteins
Many proteins can be classified into two distinct subtypes - globular or fibrous. These two types differ in their shapes and solubilities.
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...