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The control of the discrimination between dNTP and rNTP in DNA and RNA polymerase
Author(s) -
Yoon Hanwool,
Warshel Arieh
Publication year - 2016
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.25104
Subject(s) - polymerase , dna polymerase , rna polymerase , biology , dna , rna polymerase ii , biophysics , rna , genetics , chemistry , microbiology and biotechnology , computational biology , gene , gene expression , promoter
Understanding the origin of discrimination between rNTP and dNTP by DNA/RNA polymerases is important both for gaining fundamental knowledge on the corresponding systems and for advancing the design of specific drugs. This work explores the nature of this discrimination by systematic calculations of the transition state (TS) binding energy in RB69 DNA polymerase (gp43) and T7 RNA polymerase. The calculations reproduce the observed trend, in particular when they included the water contribution obtained by the water flooding approach. Our detailed study confirms the idea that the discrimination is due to the steric interaction between the 2′OH and Tyr416 in DNA polymerase, while the electrostatic interaction is the source of the discrimination in RNA polymerase. Proteins 2016; 84:1616–1624. © 2016 Wiley Periodicals, Inc.