Macromolecular Modeling and Carcinogenesis

Hoel, D G.

Abstract

This project is concerned with exploring theoretical factors involved in mutagenesis and the initial steps in carcinogenesis. Recent experimental advances in the area of genetic engineering have provided new possibilities for studying the dependence of chemically induced mutational events on DNA sequence. We hope to use computer modeling to examine the physical chemical factors (charge distribution, chemical reactivity, and stereochemical and thermodynamic relationships) contributing to site specificity of chemical agents at the level of DNA damage. An additional area of interest is the effect of amino acid substitution on protein function.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Environmental Health Sciences (NIEHS)
• Type: Intramural Research (Z01)
• Project #: 1Z01ES043010-01
• Application #: 3965252
• Support Year: 1
• Fiscal Year: 1986

Institution

• Name: U.S. National Inst of Environ Hlth Scis
• Country: United States

Publications

Min, Jungki; Perera, Lalith; Krahn, Juno M et al. (2018) Probing Dominant Negative Behavior of Glucocorticoid Receptor ? through a Hybrid Structural and Biochemical Approach. Mol Cell Biol :

Li, Yin; Perera, Lalith; Coons, Laurel A et al. (2018) Differential in Vitro Biological Action, Coregulator Interactions, and Molecular Dynamic Analysis of Bisphenol A (BPA), BPAF, and BPS Ligand-ER? Complexes. Environ Health Perspect 126:017012

Perera, Lalith; Li, Yin; Coons, Laurel A et al. (2017) Binding of bisphenol A, bisphenol AF, and bisphenol S on the androgen receptor: Coregulator recruitment and stimulation of potential interaction sites. Toxicol In Vitro 44:287-302

Perera, Lalith; Beard, William A; Pedersen, Lee G et al. (2017) Hiding in Plain Sight: The Bimetallic Magnesium Covalent Bond in Enzyme Active Sites. Inorg Chem 56:313-320

Perera, Lalith; Freudenthal, Bret D; Beard, William A et al. (2017) Revealing the role of the product metal in DNA polymerase ? catalysis. Nucleic Acids Res 45:2736-2745

Almaliti, Jehad; Al-Hamashi, Ayad A; Negmeldin, Ahmed T et al. (2016) Largazole Analogues Embodying Radical Changes in the Depsipeptide Ring: Development of a More Selective and Highly Potent Analogue. J Med Chem 59:10642-10660

Takaku, Motoki; Grimm, Sara A; Shimbo, Takashi et al. (2016) GATA3-dependent cellular reprogramming requires activation-domain dependent recruitment of a chromatin remodeler. Genome Biol 17:36

Perera, Lalith; Freudenthal, Bret D; Beard, William A et al. (2015) Requirement for transient metal ions revealed through computational analysis for DNA polymerase going in reverse. Proc Natl Acad Sci U S A 112:E5228-36

Perera, Lalith; Beard, William A; Pedersen, Lee G et al. (2014) Applications of quantum mechanical/molecular mechanical methods to the chemical insertion step of DNA and RNA polymerization. Adv Protein Chem Struct Biol 97:83-113

Perdivara, Irina; Perera, Lalith; Sricholpech, Marnisa et al. (2013) Unusual fragmentation pathways in collagen glycopeptides. J Am Soc Mass Spectrom 24:1072-81