A5082397963- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Protein Structure and Dynamics
- DNA and Nucleic Acid Chemistry
- interferon and immune responses
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- Bacterial Genetics and Biotechnology
- Topological and Geometric Data Analysis
- Advanced biosensing and bioanalysis techniques
- Machine Learning in Bioinformatics
- Image Retrieval and Classification Techniques
- Advanced Graph Neural Networks
- Genomics and Chromatin Dynamics
- Enzyme Structure and Function
Duke University
2020-2024
Crescent University
2021
Computer Algorithms for Medicine
2020
Abstract Biomolecules form dynamic ensembles of many inter-converting conformations which are key for understanding how they fold and function. However, determining is challenging because the information required to specify atomic structures thousands far exceeds that experimental measurements. We addressed this data gap dramatically simplified accelerated RNA ensemble determination by using structure prediction tools leverage growing database generate a conformation library. Refinement...
Temporal graphs effectively model dynamic systems by representing interactions as timestamped edges. However, analytical tools for temporal are limited compared to static graphs. We propose a novel method analyzing using Persistent Homology. Our approach leverages $\delta$-temporal motifs (recurrent subgraphs) capture dynamics %without aggregation . By evolving these motifs, we define the \textit{average filtration} and compute PH on associated clique complex. This captures both local global...
Abstract Sparse and short-lived excited RNA conformational states are essential players in cell physiology, disease, therapeutic development, yet determining their 3D structures remains challenging. Combining mutagenesis, NMR spectroscopy, computational modeling, we determined the structural ensemble formed by a (lifetime ~2.1 ms) lowly-populated (~0.4%) state HIV-1 TAR RNA. Through strand register shift, completely remodels structure of ground (RMSD from = 7.2 ± 0.9 Å), forming surprisingly...
Knowing the 3D structures formed by various conformations populating RNA free-energy landscape, their relative abundance, and kinetic interconversion rates is required to obtain a quantitative predictive understanding of how RNAs fold function at atomic level. While methods integrating ensemble-averaged experimental data with computational modeling are helping define most abundant in ensembles, elucidating determining sparsely populated short-lived excited conformational states (ESs) remains...
Abstract Folded RNAs contain tertiary contact motifs whose structures and energetics are conserved across different RNAs. The transferable properties of RNA simplify the folding problem, but measuring energetic conformational many remains a challenge. Here, we use high-throughput thermodynamic approach to investigate how sequence changes alter binding naturally-occurring motifs, GAAA tetraloop • receptor (TLR) interactions. We measured energies preferences TLR sequences that span mutational...
Folded RNAs contain tertiary contact motifs whose structures and energetics are conserved across different RNAs. The transferable properties of RNA simplify the folding problem, but measuring energetic conformational many remains a challenge. Here, we use high-throughput thermodynamic approach to investigate how sequence changes alter binding naturally occurring motifs, GAAA tetraloop • receptor (TLR) interactions. We measured energies preferences TLR sequences that span mutational pathways...
Cellular processes are the product of interactions between biomolecules, which associate to form biologically active complexes 1 . These mediated by intermolecular contacts, if disrupted, lead alterations in cell physiology. Nevertheless, formation contacts nearly universally requires changes conformations interacting biomolecules. As a result, binding affinity and cellular activity crucially depend not only on strength but also inherent propensities binding-competent conformational states...
Abstract Biomolecules do not fold into a single 3D structure but rather form dynamic ensembles of many inter-converting conformations 1 . Knowledge is key for understanding how biomolecules and function, rationally manipulating their activities in drug discovery synthetic biology 2–4 However, solving at atomic resolution major challenge structural because the information required to specify position all atoms thousands an ensemble far exceeds content experimental measurements. Here we...
RNAs undergo conformational adaptation upon binding to proteins and small molecules optimize inter-molecular interactions. The thermodynamic propensity of an RNA adopt a bound ensemble is important determinant the overall affinity. However, little known regarding this energetic cost because it requires measuring relative populations low-abundance short-lived conformations in apo-ensemble that may not be detectable using conventional biophysical methods. Here, NMR-derived measurements...