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.
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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 |
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