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Free energy calculation on base specificity of drug – DNA interactions: Application to daunomycin and acridine intercalation into DNA
Author(s) -
Cieplak Piotr,
Rao Shashidhar N.,
Grootenhuis Peter D. J.,
Kollman Peter A.
Publication year - 1990
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360290406
Subject(s) - chemistry , intercalation (chemistry) , acridine , dna , base pair , nucleobase , base (topology) , acridine derivatives , biophysics , combinatorial chemistry , stereochemistry , biochemistry , organic chemistry , mathematical analysis , mathematics , biology
We present the results of free energy perturbation/molecular dynamics studies on B‐DNA · daunomycin and B‐DNA · 9‐aminoacridine complexes as well as on B‐DNA itself in order to calculate the free energy differences between complexes having different base pair sequences. The results generally reproduce the trends observed experimentally, i.e., preferences of acridine and daunomycin to bind to a specific base sequence in the DNA. This is encouraging, given the simplicity of the molecular mechanical/dynamical model in which solvent is not explicitly included.