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 Email

lxue@pacific.edu

Faculty Mentor Department

Chemistry

Additional Faculty Mentor Name

Qiao-Hong Chen

Additional Faculty Mentor Email

qchen@csufresno.edu

Additional Faculty Mentor Department

Department of Chemistry, Fresno State University

Graduate Student Mentor Name

Mandeep Singh

Graduate Student Mentor Email

m_singh11@u.pacific.edu

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.