Related Experiment Video
Updated: Feb 11, 2026
15:05
Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
9.3K
Structure refinement of membrane proteins via molecular dynamics simulations.
Bercem Dutagaci1, Lim Heo1, Michael Feig1
1Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, USA.
Proteins
|April 21, 2018
Summary
A new protocol refines membrane protein structures using physics-based methods. This approach improves homology models, showing promise for understanding these vital biological molecules.
Area of Science:
- Structural Biology
- Computational Biology
- Biophysics
Background:
- Membrane proteins are crucial for cellular functions but challenging to study structurally.
- Homology modeling is a common approach for predicting membrane protein structures.
- Refinement protocols are essential for improving the accuracy of predicted protein models.
Purpose of the Study:
- To evaluate a physics-based refinement protocol for membrane protein structures.
- To compare the effectiveness of different sampling environments (lipid bilayer vs. aqueous solvent) and scoring functions.
- To assess the protocol's performance against established methods for soluble proteins.
Main Methods:
- Homology modeling was used to generate initial membrane protein structures.
- Molecular dynamics simulations were performed in explicit lipid bilayers and aqueous solvent.
- Snapshots were selected using knowledge-based (e.g., DFIRE, RWplus) and implicit membrane-based scoring functions.
- Refined models were obtained by averaging selected snapshots.
Main Results:
- The protocol achieved consistent and significant refinement of membrane protein structures.
- Refinement performance was comparable to methods used for soluble proteins.
- Sampling in lipid bilayers or aqueous solvent yielded similar refinement success.
- Knowledge-based scoring functions performed as well as implicit membrane-based functions.
Conclusions:
- The tested physics-based protocol effectively refines membrane protein homology models.
- Internal packing quality is a critical factor in refining membrane protein models.
- Lipid-facing residue improvement may benefit from sampling in lipid bilayers.
- The protocol offers a valuable tool for structural studies of membrane proteins.
Related Concept Videos
02:15Protein and Protein Structure
88.9K
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...
A protein's shape is critical to its function. For example, an enzyme...
88.9K
01:16Introduction to Membrane Proteins
81.7K
The cell membrane, or plasma membrane, is an ever-changing landscape. It is described as a fluid mosaic where various macromolecules are embedded in the phospholipid bilayer. Among the macromolecules are proteins. The protein content varies across cell types. For example, mitochondrial inner membranes contain ~76% protein content, while myelin contains ~18% protein content. Individual cells contain many types of membrane proteins—red blood cells contain over 50—and different cell...
81.7K
02:34Molecular Structure and Acidity
21.6K
An acid can be deprotonated to form a conjugate base or an anion. If the produced anion is more stable, then the acid is stronger. On the contrary, if the anion is unstable, then the acid is weaker. Hence, to determine the acidity of the compound, the stability of its conjugate base is studied using various factors.
The size effect explains the change in atomic size on acidity. When comparing the acids formed from elements that belong to the same column in the periodic table, their atomic sizes...
The size effect explains the change in atomic size on acidity. When comparing the acids formed from elements that belong to the same column in the periodic table, their atomic sizes...
21.6K
01:56Structural Protein Function
30.0K
Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
30.0K
03:00Molecular Chaperones and Protein Folding
19.9K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
19.9K
03:05Acid Strength and Molecular Structure
33.2K
Binary Acids and Bases
In the absence of any leveling effect, the acid strength of binary compounds of hydrogen with nonmetals (A) increases as the H-A bond strength decreases down a group in the periodic table. For group 17, the order of increasing acidity is HF < HCl < HBr < HI. Likewise, for group 16, the order of increasing acid strength is H2O < H2S < H2Se < H2Te. Across a row in the periodic table, the acid strength of binary hydrogen compounds increases with increasing...
In the absence of any leveling effect, the acid strength of binary compounds of hydrogen with nonmetals (A) increases as the H-A bond strength decreases down a group in the periodic table. For group 17, the order of increasing acidity is HF < HCl < HBr < HI. Likewise, for group 16, the order of increasing acid strength is H2O < H2S < H2Se < H2Te. Across a row in the periodic table, the acid strength of binary hydrogen compounds increases with increasing...
33.2K