Content area
Full Text
About the Authors:
Nuri A. Temiz
* E-mail: [email protected]
Affiliation: In Silico Research Centers of Excellence, Advanced Biomedical Computing Center, Information Systems Program, SAIC-Frederick Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America
Duncan E. Donohue
Affiliation: In Silico Research Centers of Excellence, Advanced Biomedical Computing Center, Information Systems Program, SAIC-Frederick Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America
Albino Bacolla
Current address: University of Texas at Austin, Division of Pharmacology and Toxicology, Dell Pediatric Research Institute, Austin, Texas, United States of America
Affiliations In Silico Research Centers of Excellence, Advanced Biomedical Computing Center, Information Systems Program, SAIC-Frederick Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America, Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas, United States of America
Brian T. Luke
Affiliation: In Silico Research Centers of Excellence, Advanced Biomedical Computing Center, Information Systems Program, SAIC-Frederick Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America
Jack R. Collins
Affiliation: In Silico Research Centers of Excellence, Advanced Biomedical Computing Center, Information Systems Program, SAIC-Frederick Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, United States of America
Introduction
DNA methylation is one of the main epigenetic modifications contributing to gene regulation and a considerable amount of scientific effort has been devoted to understanding the mechanisms, roles, and effects of methylation in healthy and diseased states [1]. DNA methylation has been reported to play a role in development [2], gene silencing [3], and carcinogenesis [4]. In addition, the CpG dinucleotide, which represents the main target for methylation in humans, is a known hot spot for pathological mutations [5], [6].
DNA has a flexible backbone structure characterized by fluctuations in the torsional angles α, γ, ε, ζ, and sugar pucker (δ) (See Figure 1). The α, γ angles are associated with canonical/non-canonical backbone states and ε, ζ are associated with BI and BII substates. B-DNA has been observed to prefer the BI state over the BII state in crystals and solution [7], [8]. These two states are defined by the backbone torsional angles ε and ζ (Figure 1), where ε−ζ<0 defines the BI state and ε−ζ>0 defines the BII state. These conformational ensembles are...