Abstract
Molecular recognition of DNA by small molecules and proteins is a fundamental problem in structural biology and drug design. Understanding of recognition in both sequence-selective and sequence neutral ways at the level of successful prediction of binding modes and site selectivity will be instrumental for improvements in the design and synthesis of new molecules as potent and selective gene-regulatory drugs. Minor groove is the target of a large number of non-covalent binding agents. DNA binding with specific sequences, mostly AT, takes place by means of a combination of directed hydrogen bonding to base pair edges, van der Waals interactions with the minor groove walls and generalized electrostatic interactions. These factors are also responsible for protein-DNA recognition, and a number of unifying rules governing the interactions have been elucidated although it has been realized that the earlier goal of a simple recognition code between amino acids and bases is not attainable. At present relatively little is understood about the mode of action at the molecular level of the majority of minor grooveinteracting drugs, although there is increasing evidence that they may act by directly blocking or inhibiting protein – DNA recognition. The present review has the aim to focus on interactions between minor groove binders and DNA through a variety of techniques that are commonly used to analyze the DNA binding properties of small molecules. In fact in the last years several articles dealing with in silico techniques on DNA minor groove binders (molecular modeling, molecular dynamics, QSAR) have been published. All these studies can be considered a support in defining valid predictive models. For this reason a compendium of all matter could be an useful support for future developments.
Keywords: DNA minor groove binders (mGBs), in silico techniques, molecular modeling, ab initio methods, docking, molecular dynamics simulations (MDS), QSAR, QSPR
Current Medicinal Chemistry
Title: DNA Minor Groove Binders: an Overview on Molecular Modeling and QSAR Approaches
Volume: 14 Issue: 20
Author(s): Antonino Lauria, Alessandra Montalbano, Paola Barraja, Gaetano Dattolo and Anna Maria Almerico
Affiliation:
Keywords: DNA minor groove binders (mGBs), in silico techniques, molecular modeling, ab initio methods, docking, molecular dynamics simulations (MDS), QSAR, QSPR
Abstract: Molecular recognition of DNA by small molecules and proteins is a fundamental problem in structural biology and drug design. Understanding of recognition in both sequence-selective and sequence neutral ways at the level of successful prediction of binding modes and site selectivity will be instrumental for improvements in the design and synthesis of new molecules as potent and selective gene-regulatory drugs. Minor groove is the target of a large number of non-covalent binding agents. DNA binding with specific sequences, mostly AT, takes place by means of a combination of directed hydrogen bonding to base pair edges, van der Waals interactions with the minor groove walls and generalized electrostatic interactions. These factors are also responsible for protein-DNA recognition, and a number of unifying rules governing the interactions have been elucidated although it has been realized that the earlier goal of a simple recognition code between amino acids and bases is not attainable. At present relatively little is understood about the mode of action at the molecular level of the majority of minor grooveinteracting drugs, although there is increasing evidence that they may act by directly blocking or inhibiting protein – DNA recognition. The present review has the aim to focus on interactions between minor groove binders and DNA through a variety of techniques that are commonly used to analyze the DNA binding properties of small molecules. In fact in the last years several articles dealing with in silico techniques on DNA minor groove binders (molecular modeling, molecular dynamics, QSAR) have been published. All these studies can be considered a support in defining valid predictive models. For this reason a compendium of all matter could be an useful support for future developments.
Export Options
About this article
Cite this article as:
Antonino Lauria , Alessandra Montalbano , Paola Barraja , Gaetano Dattolo and Anna Maria Almerico , DNA Minor Groove Binders: an Overview on Molecular Modeling and QSAR Approaches, Current Medicinal Chemistry 2007; 14 (20) . https://dx.doi.org/10.2174/092986707781389673
DOI https://dx.doi.org/10.2174/092986707781389673 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
The Role of Mediterranean Diet, CoQ10 and Conjugated-Melatonin in Osteoporosis Primary Prevention and Therapy
Current Nutrition & Food Science Short-Term Intra-Nasal Erythropoietin Administration with Low Sialic Acid Content is without Toxicity or Erythropoietic Effects
Current Neurovascular Research Meet Our Editor:
Current Molecular Medicine Analysis of Anticancer Drugs and their Metabolites by Mass Spectrometry
Current Drug Metabolism Intraperitoneal Oncolytic and Tumor Vaccination Therapy with Replication-Competent Recombinant Virus: The Herpes Paradigm
Current Gene Therapy α-Galactosylceramide: Potential Immunomodulatory Activity and Future Application [General Articles]
Current Medicinal Chemistry Inhibition of TGF- Signaling for the Treatment of Tumor Metastasis and Fibrotic Diseases
Current Signal Transduction Therapy Targeting Cytokines, Chemokines and Adhesion Molecules in Rheumatoid Arthritis
Current Rheumatology Reviews Progress in the Development of Bestatin Analogues as Aminopeptidases Inhibitors
Current Medicinal Chemistry Human Immunodeficiency Virus-Associated Malignancies: A Therapeutic Update
Current HIV Research Metabolic and Cardiovascular Ageing Indices in Relation to Glycated Haemoglobin in Healthy and Diabetic Subjects
Current Aging Science Herpes Simplex Encephalitis: From Virus to Therapy
Infectious Disorders - Drug Targets Patent Selections:
Recent Patents on Inflammation & Allergy Drug Discovery PRAME/EZH2-Mediated Regulation of TRAIL: A New Target for Cancer Therapy
Current Molecular Medicine Effective Delivery of Male Contraceptives Behind the Blood-Testis Barrier (BTB) – Lesson from Adjudin
Current Medicinal Chemistry Evaluation of Antidiabetic Activity of <i>Rosmarinus officinalis var. prostratus</i> Growing in Syria in Alloxan Diabetic Rats
Current Bioactive Compounds Role of Matrix Metalloproteinases in Animal Models of Ischemic Stroke
Current Vascular Pharmacology From Alpha to Omega with Aβ: Targeting the Multiple Molecular Appearances of the Pathogenic Peptide in Alzheimers Disease
Current Medicinal Chemistry Translational Optical Imaging in Diagnosis and Treatment of Cancer
Current Pharmaceutical Biotechnology Glutamate and Mitochondria: Two Prominent Players in the Oxidative Stress-Induced Neurodegeneration
Current Alzheimer Research