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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Apigenin-mediated Alterations in Viability and Senescence of SW480 Colorectal Cancer Cells Persist in The Presence of L-thyroxine
Anti-Cancer Agents in Medicinal Chemistry IGF-I Abuse in Sport
Current Drug Abuse Reviews Photodynamic Therapy using Carbohydrate Conjugated Porphyrins
Drug Design Reviews - Online (Discontinued) Perspectives Offered by Single-Domain Antibodies in Clinical Diagnostic of Pediatric Tumors
Current Medicinal Chemistry Epigenetic and Disease Targets by Polyphenols
Current Pharmaceutical Design Management of Gestational Trophoblastic Diseases-An Update
Reviews on Recent Clinical Trials The PKB/AKT Pathway in Cancer
Current Pharmaceutical Design Molecular Pathways of Interferon-Stimulated Gene 15: Implications in Cancer
Current Protein & Peptide Science Highlights in Peptide Nanoparticle Carriers Intended to Oral Diseases
Current Topics in Medicinal Chemistry Recent Patents on Liposomal-Based Chemotherapeutics with a Triggered Release Mechanism
Recent Patents on Nanomedicine Natural Sirtuin Modulators in Drug Discovery: A Review (2010 -2020)
Current Medicinal Chemistry Targeted Cancer Therapy; Nanotechnology Approaches for Overcoming Drug Resistance
Current Medicinal Chemistry In Vitro Synergistic Interaction Between Amide Piplartine and Antimicrobial Peptide Dermaseptin Against Schistosoma mansoni Schistosomula and Adult Worms
Current Medicinal Chemistry Cancer T Cell Immunotherapy with Bispecific Antibodies and Chimeric Antigen Receptors
Recent Patents on Anti-Cancer Drug Discovery Current Pharmacological Approaches to Prevent and Treat Post- Menopausal Osteoporosis
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Physiological Functions of Presenilins; Beyond γ-Secretase
Current Pharmaceutical Biotechnology Hormone Replacement Therapy and Stroke
Current Vascular Pharmacology Prostaglandin E Synthase: A Novel Drug Target for Inflammation and Cancer
Current Pharmaceutical Design Beyond PD-1/PD-L1 Axis Blockade: New Combination Strategies in Metastatic Melanoma Treatment
Current Cancer Therapy Reviews Silver and Other Metals in the Treatment of Gastrointestinal Diseases
Current Medicinal Chemistry