Title

Binding of Flavonoid Derivatives to G-Quadruplex DNA Studied by Molecular Docking

Poster Number

18C

Lead Author Major

Biochemistry

Lead Author Status

Junior

Format

Poster Presentation

Faculty Mentor Name

Liang Xue

Faculty Mentor Department

Chemistry

Additional Faculty Mentor Name

Qiao-Hong Chen

Additional Faculty Mentor Department

Department of Chemistry, Fresno State University

Graduate Student Mentor Name

Mandeep Singh

Graduate Student Mentor Department

Chemistry

Additional Mentors

Graduate Student Mentor Name: Vanessa Rangel

Graduate Student Mentor Email: v_rangel1@u.pacific.edu

Graduate Student Mentor Department: Department of Chemistry, University of the Pacific

Abstract/Artist Statement

Four guanines self-assemble into a planar G-quartet structure via Hoogsteen H-bonding. Several G-quartets can stack on top of each other to form a unique DNA secondary structure – G-quadruplex. Over 300,000 G-quadruplex forming sequences are present in the human genome including the telomere region. The telomeres are single-stranded tails at the end of chromosomes that provide protection against nucleases and genomic degradation. The telomere region shortens with every cell division, eventually reaching a critical point resulting in cell death. The telomere length is maintained in 80-90% of cancer cells by a reverse transcriptase (telomerase) that adds telomeric DNA fragments to the chromosome ends. Such continuous telomere extension results in “immortal” cell growth and replication, a characteristic of cancer. Because of this, telomerase in recent years has become a promising anti-cancer target. It is well known that the formation of G-quadruplexes in telomeres inhibits the activity of telomerase. Small molecules that can facilitate G-quadruplex formation have been developed as potential anti-cancer drugs. In the present work, we studied the binding of novel flavonoid derivatives to various G-quadruple DNA using computational tools. G-quadruplexes with different conformations including parallel, anti-parallel, and hybrid-type were used. Programs such as Spartan and ChemDraw3D were used for the creation of digital ligands, and AutoDockTools and Autodock Vina were used for finding probable and stable ligand-DNA conformations to determine the binding efficiency and stability. The preliminary calculations indicate that planar ligands, especially ring-based ligands, prefer to stack with the end G-quartets, while the sidechains fold into the large grooves between the DNA backbones. Planar ligands bind more effectively with parallel G-quadruplexes than anti-parallel and hybrid-type G-quadruplexes. Biophysical studies of the effective ligands identified from docking results with G-quadruplex DNA will be conducted in the future.

Location

DeRosa University Center Ballroom

Start Date

27-4-2018 10:00 AM

End Date

27-4-2018 12:00 PM

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Apr 27th, 10:00 AM Apr 27th, 12:00 PM

Binding of Flavonoid Derivatives to G-Quadruplex DNA Studied by Molecular Docking

DeRosa University Center Ballroom

Four guanines self-assemble into a planar G-quartet structure via Hoogsteen H-bonding. Several G-quartets can stack on top of each other to form a unique DNA secondary structure – G-quadruplex. Over 300,000 G-quadruplex forming sequences are present in the human genome including the telomere region. The telomeres are single-stranded tails at the end of chromosomes that provide protection against nucleases and genomic degradation. The telomere region shortens with every cell division, eventually reaching a critical point resulting in cell death. The telomere length is maintained in 80-90% of cancer cells by a reverse transcriptase (telomerase) that adds telomeric DNA fragments to the chromosome ends. Such continuous telomere extension results in “immortal” cell growth and replication, a characteristic of cancer. Because of this, telomerase in recent years has become a promising anti-cancer target. It is well known that the formation of G-quadruplexes in telomeres inhibits the activity of telomerase. Small molecules that can facilitate G-quadruplex formation have been developed as potential anti-cancer drugs. In the present work, we studied the binding of novel flavonoid derivatives to various G-quadruple DNA using computational tools. G-quadruplexes with different conformations including parallel, anti-parallel, and hybrid-type were used. Programs such as Spartan and ChemDraw3D were used for the creation of digital ligands, and AutoDockTools and Autodock Vina were used for finding probable and stable ligand-DNA conformations to determine the binding efficiency and stability. The preliminary calculations indicate that planar ligands, especially ring-based ligands, prefer to stack with the end G-quartets, while the sidechains fold into the large grooves between the DNA backbones. Planar ligands bind more effectively with parallel G-quadruplexes than anti-parallel and hybrid-type G-quadruplexes. Biophysical studies of the effective ligands identified from docking results with G-quadruplex DNA will be conducted in the future.