Abstract
Non-covalent interactions like hydrogen bonding, hydrophobic interactions and salt bridges, have been our primary focus in designing and optimizing drugs. Recently, there is mounting evidence that non-covalent interactions involving aromatic rings are also potent forces for the recognition between small drug-like compounds and their targets. Understanding of these interactions and their physical origin is of significant interest for improving the current drug design strategy. Hence, numerous efforts have been devoted to elucidating the structural, geometrical, energetic, and thermodynamic properties of these interactions, which include π-π, cation-π and anion-πinteractions. In this review, we established a framework to systematically understand the structural basis and physicochemical properties of the aromatic interactions at the binding interface of protein-ligand complexes. Firstly, we presented an introduction including the definition, universality, energy components, geometry conformations and substituent effects of these interactions. Secondly, we retrospected the widely employed computational approaches for studying these interactions, including quantum mechanical calculations and crystallographic data mining. Finally, we illustrated with several representative protein-ligand systems to show how the aromatic interactions contribute to the design and optimization of ligand in both affinity and specificity.
Keywords: π-π interactions, cation-π, anion-π interactions, quantum mechanical calculations, crystallographic data mining, rational drug design, Acetylcholine esterase (AChE), HMG-CoA reductase (HMGR), serine protease factor Xa (fXa).
Current Pharmaceutical Design
Title:Non-Covalent Interactions with Aromatic Rings: Current Understanding and Implications for Rational Drug Design
Volume: 19 Issue: 36
Author(s): Shanshan Li, Yuan Xu, Qiancheng Shen, Xian Liu, Jing Lu, Yadong Chen, Tao Lu, Cheng Luo, Xiaomin Luo, Mingyue Zheng and Hualiang Jiang
Affiliation:
Keywords: π-π interactions, cation-π, anion-π interactions, quantum mechanical calculations, crystallographic data mining, rational drug design, Acetylcholine esterase (AChE), HMG-CoA reductase (HMGR), serine protease factor Xa (fXa).
Abstract: Non-covalent interactions like hydrogen bonding, hydrophobic interactions and salt bridges, have been our primary focus in designing and optimizing drugs. Recently, there is mounting evidence that non-covalent interactions involving aromatic rings are also potent forces for the recognition between small drug-like compounds and their targets. Understanding of these interactions and their physical origin is of significant interest for improving the current drug design strategy. Hence, numerous efforts have been devoted to elucidating the structural, geometrical, energetic, and thermodynamic properties of these interactions, which include π-π, cation-π and anion-πinteractions. In this review, we established a framework to systematically understand the structural basis and physicochemical properties of the aromatic interactions at the binding interface of protein-ligand complexes. Firstly, we presented an introduction including the definition, universality, energy components, geometry conformations and substituent effects of these interactions. Secondly, we retrospected the widely employed computational approaches for studying these interactions, including quantum mechanical calculations and crystallographic data mining. Finally, we illustrated with several representative protein-ligand systems to show how the aromatic interactions contribute to the design and optimization of ligand in both affinity and specificity.
Export Options
About this article
Cite this article as:
Li Shanshan, Xu Yuan, Shen Qiancheng, Liu Xian, Lu Jing, Chen Yadong, Lu Tao, Luo Cheng, Luo Xiaomin, Zheng Mingyue and Jiang Hualiang, Non-Covalent Interactions with Aromatic Rings: Current Understanding and Implications for Rational Drug Design, Current Pharmaceutical Design 2013; 19 (36) . https://dx.doi.org/10.2174/13816128113199990440
DOI https://dx.doi.org/10.2174/13816128113199990440 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Cationicity and Hydrophobicity Enhance the Cytotoxic Potency of Phoratoxin C Anticancer Peptide Analogues against Triple Negative Breast Cancer Cells
Current Bioactive Compounds Prader-Willi Syndrome: Molecular Mechanism and Epigenetic Therapy
Current Gene Therapy Anabolic-androgenic Steroid use and Psychopathology in Athletes. A Systematic Review
Current Neuropharmacology Castor Oil Based Multifunctional Greener Additives for Lubricating Oil
Current Environmental Engineering Evolving Mechanistic Concepts of Epileptiform Synchronization and their Relevance in Curing Focal Epileptic Disorders
Current Neuropharmacology Disruptive Nanozyme Technology for Futuristic Bio-Medical and Bio-imaging Applications
Current Nanoscience Statins and Protein Prenylation in Cancer Cell Biology and Therapy
Anti-Cancer Agents in Medicinal Chemistry Neurostimulation in Clinical and Sub-clinical Eating Disorders: A Systematic Update of the Literature
Current Neuropharmacology Effect of Nigella Sativa and Allium Sativum Coadminstered with Simvastatin in Dyslipidemia Patients: A Prospective, Randomized, Double-Blind Trial
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Role and Treatment of Mitochondrial DNA-Related Mitochondrial Dysfunction in Sporadic Neurodegenerative Diseases
Current Pharmaceutical Design Therapeutic Perspectives in Alzheimers Disease
Recent Patents on CNS Drug Discovery (Discontinued) Releasing the Genie in the Bottle: Molecular Signaling with Hydrogen Sulfide
Current Neurovascular Research Amelioration of Myocardial Ischemic Reperfusion Injury with Calendula Officinalis
Current Pharmaceutical Biotechnology Nociceptin /Orphanin FQ Peptide (NOP) Receptor Modulators: An Update in Structure-Activity Relationships
Current Medicinal Chemistry Crystal Structures of Phosphodiesterases and Implications on Substrate Specificity and Inhibitor Selectivity
Current Topics in Medicinal Chemistry Therapeutic Implications of Immunoparalysis in Critically Ill Patients
Inflammation & Allergy - Drug Targets (Discontinued) Inulin as a Delivery Vehicle for Targeting Colon-Specific Cancer
Current Drug Delivery Pharmacotherapy for Late-Life Depression with Psychotic Features: A Review of Literature of Randomized Control Trials
Current Psychiatry Reviews Mycotoxin Exposure and Autism: A Systematic Review of the Molecular Mechanism
Current Molecular Pharmacology Conference Report: 182nd AAAS Annual Meeting, Washington DC, February 11-15, 2016
CNS & Neurological Disorders - Drug Targets