title: Why does β-cyclodextrin prefer to bind nucleotides with an adenine base rather than other 2'-deoxyribonucleoside 5'-monophosphates?
abstract: β-Cyclodextrin (β-CD), which resides in the α-hemolysin (αHL) protein pore, can act as a molecular adapter in single-molecule exonuclease DNA sequencing approaches, where the different nucleotide binding behavior of β-CD is crucial for base discrimination. In the present contribution, the inclusion modes of β-CD towards four 2'-deoxyribonucleoside 5'-monophosphates (dNMPs) were investigated using quantum mechanics (QM) calculations. The calculated binding energy suggests that the binding affinity of dAMP to β-CD are highest among all the dNMPs in solution, in agreement with experimental results. Geometry analysis shows that β-CD in the dAMP complex undergoes a small conformational change, and weak interaction analysis indicates that there are small steric repulsion regions in β-CD. These results suggest that β-CD has lower geometric deformation energy in complexation with dAMP. Furthermore, topological analysis and weak interaction analysis suggest that the number and strength of intermolecular hydrogen bonds and van der Waals interactions are critical to dAMP binding, and they both make favorable contributions to the lower interaction energy. This work reveals the reason why β-CD prefers to bind dAMP rather than other dNMPs, while opening exciting perspectives for the design of novel β-CD-based molecular adapters in the single-molecule exonuclease method of sequencing DNA. Graphical Abstract The binding affinity of β-cyclodextrin towards four 2'-deoxyribonucleoside 5'-monophosphates was investigated using quantum mechanics calculations.
authors.affiliation: College of Radiation, Taishan Medical University, Taian, 271016, People's Republic of China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: College of Chemistry and Chemical Engineering, Taishan University, Taian, 271021, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liu
authors.affiliation: College of Chemistry and Pharmaceutical Engineering, Taishan Medical University, Taian, 271016, People's Republic of China. wangteng@mail.nankai.edu.cn.
authors.forename: Teng
authors.identifier: http://orcid.org/0000-0002-8422-6781
authors.initials: T
authors.lastname: Wang
authors.affiliation: College of Chemistry and Pharmaceutical Engineering, Taishan Medical University, Taian, 271016, People's Republic of China.
authors.forename: Liping
authors.initials: L
authors.lastname: Sun
mesh_terms: D003198:Computer Simulation; D003838:Deoxyadenine Nucleotides / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D011789:Quantum Theory; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D003838:Deoxyadenine Nucleotides; D047392:beta-Cyclodextrins; C012873:2'-deoxy-5'-adenosine monophosphate
keywords: Cyclodextrin; Density functional theory; Nonconvalent weak interaction; Nucleotide; Quantum mechanics