| nmrlearner |
03-15-2005 08:09 AM |
Project description from Dr. Patel's website: - NMR Methods Development
Our efforts have focused on enhancing isotope labeling methods to aid NMR resonance assignments, coupling constant methods to identify hydrogen bonding alignments, and residual dipolar coupling approaches to speed RNA resonance assignments and monitor junctional architecture and helical dynamics.
- RNA Architecture and Dynamics
Our laboratory has initiated a major program to structurally characterize higher order RNA architecture and dynamics using NMR and x-ray crystallography. Current efforts are focused on RNA triplet repeat disease sequences, internal loops, pseudoknots, and junctions.
- Peptide-RNA Recognition: Viral and Phage Systems
This project is focused on the structural characterization of the novel folds of bound arginine-rich peptides and the architecture of their RNA binding pockets in viral and phage systems. These studies are based on an approach where the components are minimalist modular domains that undergo adaptive structural transitions on complex formation.
- Saccharide-RNA Recognition: Aminoglycoside Antibiotics
Aminoglycoside antibiotics are polycationic saccharides that exhibit therapeutic potential against bacterial infections. Functionally, they interfere with translation and induce bacterial cell death through site-specific targeting of ribosomal 16S RNA. Our research has focused on aminoglycoside antibiotic-RNA complexes, involving tobramycin, neomycin B, apramycin, and streptomycin.
- Adaptive Recognition in RNA and DNA Aptamers: Cofactors and Amino Acids
Novel features of nucleic acid structure, recognition, and discrimination have been elucidated through the solution structural characterization of RNA and DNA aptamers that bind cofactors and amino acids with high affinity and specificity. The cofactors include ATP and FMN, while the amino acid studies have focused on argininamide.
- Protein-RNA Recognition
This new effort focuses on the crystallographic characterisation of protein-RNA complexes to elucidate the principles associated with molecular recognition. Several areas under current investigation include complexes that participate in RNA translation, transport, localization, and splicing.
- Multi-stranded DNA Architectures: Triads, Tetrads, and Hexads
This project is focused on the structure and recognition of multi-stranded DNA architectures adopted by guanine plus adenine rich sequences. Such guanine plus adenine rich sequences are frequently located within gene regulatory regions and recombination hot spot sites at the replication origin of single-stranded bacteriophages, and as tandem repeats in telomeric, centromeric, and triplet repeat disease sequences.
- Antitumor Drug-DNA Complexes
This program seeks to elucidate the structure of antitumor drugs bound to their sequence specific sites on DNA duplexes, triplexes, and quadruplexes. The emphasis here is to identify the principles of stacking, hydrogen bonding, and hydrophobic interactions that contribute to the specificity and affinity associated with molecular recognition.
- Covalent Carcinogenic DNA Adducts
Human DNA is continuously exposed to a variety of metabolically activated chemical intermediates that react covalently with nucleic acids to form adducts that locally perturb the architecture of duplex DNA. Our studies have focused on structural elucidation of adduct alignment as a function of chirality and sequence context.
- Protein Structure and Recognition
This program is a collaborative effort with colleagues at Sloan-Kettering to elucidate protein structures and their complexes. Current efforts are in the area of proteins involved in leukemia, DNA repair, and viral pathogenesis.
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