Abstract
In drug design and enzyme engineering, the information of interactions between receptors and ligands is crucially important. In many cases, the protein structures and drug-target complex structures are determined by a delicate balance of several weak molecular interaction types. Among these interaction forces several unconventional interactions play important roles, however, less familiar for researchers. The cation-π interaction is a unique noncovalent interaction only acting between aromatic amino acids and organic cations (protonated amino acids) and inorganic cations (proton and metallic). This article reports new study results in the interaction strength, the behaviors and the structural characters of cation-π interactions between aromatic amino acids (Phe, Tyr, and Trp) and organic and inorganic cations (Lys+, Arg+, H+, H3O+, Li+, Na+, K+, Ca2+, and Zn2+) in gas phase and in solutions (water, acetonitrile, and cyclohexane). Systematical research revealed that the cation-π interactions are point-to-plane (aromatic group) interactions, distance and orientationdependent, and the interaction energies change in a broad range. In gas phase the cation-π interaction energies between aromatic amino acids (Phe, Tyr, and Trp) and metallic cations (Li+, Na+, K+, Ca2+, and Zn2+) are in the range -12 to -160 kcal/mol, and the interaction energies of protonated amino acids (Arg+ and Lys+) are in the range from -9 to -18 kcal/mol. In solutions the cation-π energies decrease with the dielectric constant ε of solvents. However, in aqueous solution the cation-π energies of H3O+ and protonated amino acids are less affected by solvation effects. The applications of unconventional interaction forces in drug design and in protein engineering are introduced.
Keywords: Ligand-host interaction, aromatic amino acids, protein structure, drug design, organic cations, cation-π interaction, amino acids, quantum chemistry, metallic cations.
Current Topics in Medicinal Chemistry
Title:Unconventional Interaction Forces in Protein and Protein-ligand Systems and their Impacts to Drug Design
Volume: 13 Issue: 10
Author(s): Qing-Yan Wang, Jian Lu, Si-Ming Liao, Qi-Shi Du and Ri-Bo Huang
Affiliation:
Keywords: Ligand-host interaction, aromatic amino acids, protein structure, drug design, organic cations, cation-π interaction, amino acids, quantum chemistry, metallic cations.
Abstract: In drug design and enzyme engineering, the information of interactions between receptors and ligands is crucially important. In many cases, the protein structures and drug-target complex structures are determined by a delicate balance of several weak molecular interaction types. Among these interaction forces several unconventional interactions play important roles, however, less familiar for researchers. The cation-π interaction is a unique noncovalent interaction only acting between aromatic amino acids and organic cations (protonated amino acids) and inorganic cations (proton and metallic). This article reports new study results in the interaction strength, the behaviors and the structural characters of cation-π interactions between aromatic amino acids (Phe, Tyr, and Trp) and organic and inorganic cations (Lys+, Arg+, H+, H3O+, Li+, Na+, K+, Ca2+, and Zn2+) in gas phase and in solutions (water, acetonitrile, and cyclohexane). Systematical research revealed that the cation-π interactions are point-to-plane (aromatic group) interactions, distance and orientationdependent, and the interaction energies change in a broad range. In gas phase the cation-π interaction energies between aromatic amino acids (Phe, Tyr, and Trp) and metallic cations (Li+, Na+, K+, Ca2+, and Zn2+) are in the range -12 to -160 kcal/mol, and the interaction energies of protonated amino acids (Arg+ and Lys+) are in the range from -9 to -18 kcal/mol. In solutions the cation-π energies decrease with the dielectric constant ε of solvents. However, in aqueous solution the cation-π energies of H3O+ and protonated amino acids are less affected by solvation effects. The applications of unconventional interaction forces in drug design and in protein engineering are introduced.
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Cite this article as:
Wang Qing-Yan, Lu Jian, Liao Si-Ming, Du Qi-Shi and Huang Ri-Bo, Unconventional Interaction Forces in Protein and Protein-ligand Systems and their Impacts to Drug Design, Current Topics in Medicinal Chemistry 2013; 13 (10) . https://dx.doi.org/10.2174/15680266113139990002
DOI https://dx.doi.org/10.2174/15680266113139990002 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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