The Role of Protein Structure in Genomics

Abstract

MicroArrays of Gel Immobilized Compounds on a Chip (MAGIChipsTM)are produced by immobilizing oligonucleotides, DNA, enzymes, antibodies, and other compounds on a photopolymerized micromatrix of polyacrylamide gel pads 1OOX1OOX20 pm and smaller in size. Alternatively, allyl-modified compounds can be embedded within polyacrylamide gel pads by copolymerization. MAGIChips have been shown to be efficient for analysis of nucleic acid hybridization, specific binding of DNA with proteins, and low-molecular-weight compounds, and proteinprotein interactions. The three-dimensional gel pads of the microarrays can be used as nanoliter-sized microtest tubes to perform ligation, singlebase extension, PCR amplification of DNA, and other reactions. The fluorescence microscope has been devised for analyzing reactions on MAGIChips, including quantitative and real-time monitoring of hybridization, measuring the thermodynamic parameters of DNA duplexes containing different modified nucleotides, and measuring the kinetics of enzymatic reaction. On-chip MALDI-TOF mass spectrometry was successfully tested for analysis of DNA and protein interactions. Application of these biochips for detection of human polymorphism and mutations, identification of microorganisms and their drug resistant and toxin-bearing strains, and in different fields of biotechnology and medicine will be described.

Relating Protein Structure and Function Through a Bijection and Its Implications on Protein Structure Prediction

“…Knowledge-based model generators and evaluators assume surjective relations between structure and activity, since the common idea of modellers of protein 3D structures is to assist in the grouping of protein structures based on similar attributes (Gerstein & Hegyi, 1998;Domingues et al, 2000;Skolnick et al, 2000). Therefore, in these cases knowledge of the protein 3D structure may provide inaccurate information about the activity (Martin et al, 1998).…”

Conformation biases of amino acids based on tripeptide microenvironment from PDB database

“…Efforts are underway to understand the role of gene products in biological pathways and human disease and to exploit their functional roles to derive protein therapeutics and proteinbased drugs (Maggio and Ramnarayan, 2001;Domingues et al, 2000). The formations of stable secondary structures and a unique tertiary structure of proteins are dictated by intra-molecular interactions between the constituent amino acid residues along the polypeptide chain as well as their interaction with the surrounding medium.…”

Incorporation of ethical and societal issues in biochemistry into a senior seminar course

“…In several sentences each, the students are asked to respond to the following. [12] Trinucleotide repeat disorders [13] Gene replacement, gene therapy, and ethics [14][15][16] Ribozymes [17] Functional genomics [18] Protein structure/function Prions [19] Protein structure and genomics, ethical considerations [20,21] Metalloproteinase inhibitors [22] Catalytic antibodies [23] Apoptosis/cancer/AIDS Apoptosis [24] Telomerase [25] Clinical resistance to cancer therapy [26] HIV therapy [27] Neurochemistry Long term potentiation [28] Alzheimer's disease [29] Drugs of abuse [10,30] Psychological disorders [11] 4. Describe any ethical issues or societal concerns that are raised in the paper.…”