NLM DIR Seminar Schedule
UPCOMING SEMINARS
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May 2, 2025 Pascal Mutz
Characterization of covalently closed cirular RNAs detected in (meta)transcriptomic data -
May 2, 2025 Dr. Lang Wu
Integration of multi-omics data in epidemiologic research -
May 6, 2025 Leslie Ronish
TBD -
May 8, 2025 MG Hirsch
TBD -
May 13, 2025 Harutyun Saakyan
TBD
RECENT SEMINARS
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April 22, 2025 Stanley Liang, PhD
Large Vision Model for medical knowledge adaptation -
April 18, 2025 Valentina Boeva, Department of Computer Science, ETH Zurich
Decoding tumor heterogeneity: computational methods for scRNA-seq and spatial omics -
April 8, 2025 Jaya Srivastava
Leveraging a deep learning model to assess the impact of regulatory variants on traits and diseases -
April 1, 2025 Roman Kogay
Horizontal transfer of bacterial operons into eukaryote genomes -
March 25, 2025 Yifan Yang
Adversarial Manipulation and Data Memorization in Large Language Models for Medicine
Scheduled Seminars on April 27, 2023
Contact NLMDIRSeminarScheduling@mail.nih.gov with questions about this seminar.
Abstract:
Although homologous protein sequences are expected to adopt similar structures, some amino acid substitutions can interconvert α-helices and β-sheets. Such fold switching may have occurred over evolutionary history, but supporting evidence has been limited by the: (1) abundance and diversity of sequenced genes, (2) quantity of experimentally determined protein structures, and (3) assumptions underlying the statistical methods used to infer homology. Here, we overcame these barriers by applying multiple statistical methods to a family of ~600,000 bacterial response regulator proteins. We found that their homologous DNA-binding subunits assume divergent structures: helix-turn-helix versus α-helix+β-sheet (winged helix). Phylogenetic analyses, ancestral sequence reconstruction, and AlphaFold2 models indicated that amino acid substitutions facilitated a switch from helix-turn-helix into winged helix. This structural transformation likely expanded DNA-binding specificity. Our approach uncovers an evolutionary pathway between two protein folds and provides methodology to identify secondary structure switching in other protein families.