Paper Info
Title
Setting Anchor in the Minor Groove: in Silico Investigation into Formamido N-Methylpyrrole and N-Methylimidazole Polyamides Bound by Cognate DNA Sequences.
Abstract
Tricyclic N-methylpyrrole (Py) and N-methylimidazole (Im) containing polyamide monocations are known to bind as stacked dimers within the minor groove of DNA, and those with N-terminal formamido (f) substituents bind in a staggered configuration with high specificity over a range of affinities. Although binding constants have been reported, there is not a clear understanding of why such constants vary significantly for polyamide dimers and their respective cognate DNA sequences. By employing computational tools, the following homodimer complexes have been addressed in this study: f-PyPyIm in complex with 5'-d(GAACTAGTTC)-3', f-ImPyPy in complex with 5'-d(GAATGCATTC)-3', and f-ImPyIm in complex with 5'-d(GAACGCGTTC)-3'. These complexes were selected based on their 10- to 100-fold differences in binding constants. From this study, it was possible to determine how polyamides anchor themselves within the minor groove of specific DNA sequences. This is clone through several interactions that provide stability for specific recognition: (i) Py groups secure themselves between DNA base pairs, (ii) lone-pair-Pi interactions are formed between DNA deoxyribose 04' and Im groups nearest f, (iii) minor groove bases hydrogen bond to Im groups and amides of the polyamide backbone, (iv) f substituents rotate without leaving the minor groove of DNA and with this rotation form specific hydrogen bonds with electron-rich sites on the floor of the minor groove, and (v) flexible charged N,N-dimethylaminoalkyl substituents reside favorably in the minor groove of DNA. Results displayed the greatest amount of interactions and stability for dimeif-ImPylm in complex with 5'-d(GAACGCGTTC)-3' and the least amount in dimer f-PyPyIm in complex with 5'-d(GAACTAGYTC)-3'. Hence, for cognate DNA sequences, the relative binding strength of compounds was determined as f-ImPyIm > f-ImPyPy > f-PyPyIm. This force-field-based computational study is in agreement with experimental results and provides a molecular rational for the binding constant values.
Year
DOI
Venue
2010
10.1021/ci100191a
JOURNAL OF CHEMICAL INFORMATION AND MODELING
Keywords
Field
DocType
dna sequence,base pair,force field,hydrogen bond,n terminal
Groove (music),Polyamide,Chemistry,DNA,N-methylimidazole,DNA sequencing,Stereochemistry,Hydrogen bond,Affinities,In silico
Journal
Volume
Issue
ISSN
50
9
1549-9596
Citations 
PageRank 
References 
0
0.34
0
Authors
3
Name
Order
Citations
PageRank
Catharine Collar1111.34
Moses Lee200.34
W. David Wilson300.34