10 Applications of Molecular Dynamics Simulations …
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10.5.2 Preparation of the Protein Structure
After the initial 3D structure is obtained, the following steps should be carried out
before the energy minimization.
1. Remove the redundant atoms: The experimentally determined 3D structure of
a protein might be in the dimeric or multimeric form with stabilizing chemical
agents from the structure determination. Here, the monomer of the protein is
extracted from the multimeric form of the protein. The small atoms or chemical
agents which are not paramount to protein function should be removed.
2. Add missing residues and atoms: Some proteins from PDB might lack residues
or atoms in their coordinate files. Hence, it is important to cross-check whether
the selected protein structure has any missing residues or atoms. Once missing
residues or atoms are found, the missing regions should be rebuilt using computational software. After the missing residues or atoms are rebuilt in the structure,
hydrogen atoms should be added and the protonation states should be assigned
ionizable residues such as arginine, glutamate, lysine, aspartate, and histidine
which play a very important role in most of the protein functions.
3. Replace mutated atoms: During crystallization, some protein–ligand complexes
are not able to form a stable structure. Thus, some residues in a protein complex
were mutated to obtain a stable complex. Such residues should be replaced by
the appropriate native residues.
10.5.3 Generating Topology and Parameter Files
The topological file for a given protein contains all geometric information including
angles, bonds, and interactions. Once the protein is prepared, it is next important
to generate the topology files for the protein and small molecules by applying the
appropriate force field [60–65]. Sometimes, the topology file combines the parameter
files (describing the potential energy of the systems) that are generated by applying
the chosen force field. Various force fields have been developed for proteins, lipids,
nucleic acids, carbohydrates, and small molecules. The force field selection is guided
by the nature of the protein and the purpose of the research. There are various utilities
to generate the topology files for small molecules which are compatible for most MD
simulation programs.
10.5.4 Solvating the System
Explicit and implicit models are two different water models simulating a protein or
a protein complex in an aqueous solution. The implicit solvent model is efficient and
yields a reasonable description of the behavior of the solvent but fails to provide
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10.5.2 Preparation of the Protein Structure
After the initial 3D structure is obtained, the following steps should be carried out
before the energy minimization.
1. Remove the redundant atoms: The experimentally determined 3D structure of
a protein might be in the dimeric or multimeric form with stabilizing chemical
agents from the structure determination. Here, the monomer of the protein is
extracted from the multimeric form of the protein. The small atoms or chemical
agents which are not paramount to protein function should be removed.
2. Add missing residues and atoms: Some proteins from PDB might lack residues
or atoms in their coordinate files. Hence, it is important to cross-check whether
the selected protein structure has any missing residues or atoms. Once missing
residues or atoms are found, the missing regions should be rebuilt using computational software. After the missing residues or atoms are rebuilt in the structure,
hydrogen atoms should be added and the protonation states should be assigned
ionizable residues such as arginine, glutamate, lysine, aspartate, and histidine
which play a very important role in most of the protein functions.
3. Replace mutated atoms: During crystallization, some protein–ligand complexes
are not able to form a stable structure. Thus, some residues in a protein complex
were mutated to obtain a stable complex. Such residues should be replaced by
the appropriate native residues.
10.5.3 Generating Topology and Parameter Files
The topological file for a given protein contains all geometric information including
angles, bonds, and interactions. Once the protein is prepared, it is next important
to generate the topology files for the protein and small molecules by applying the
appropriate force field [60–65]. Sometimes, the topology file combines the parameter
files (describing the potential energy of the systems) that are generated by applying
the chosen force field. Various force fields have been developed for proteins, lipids,
nucleic acids, carbohydrates, and small molecules. The force field selection is guided
by the nature of the protein and the purpose of the research. There are various utilities
to generate the topology files for small molecules which are compatible for most MD
simulation programs.
10.5.4 Solvating the System
Explicit and implicit models are two different water models simulating a protein or
a protein complex in an aqueous solution. The implicit solvent model is efficient and
yields a reasonable description of the behavior of the solvent but fails to provide