NLM IRP Seminar Schedule
UPCOMING SEMINARS
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April 30, 2024 Wenya Rowe
The conformal central charge of the spin-1/2 XX model derived from long-chain asymptotics -
May 2, 2024 OPEN
TBD -
May 7, 2024 OPEN
TBD -
May 9, 2024 Pascal Mutz
TBD -
May 14, 2024 Stanley Liang
TBD
RECENT SEMINARS
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April 25, 2024 Ermin Hodzic
Condition-Aware Cell Type Deconvolution of Bulk Tissues -
April 23, 2024 OPEN
TBD -
April 16, 2024 Jaya Srivastava
Regulatory plasticity of the human genome -
April 11, 2024 Sergey Shmakov
Comprehensive survey of the TnpB RNA-guided nucleases -
April 2, 2024 Yifan Yang
Fairness and Bias in Biomedical AI
Scheduled Seminars on March 28, 2024
Contact NLM_IRP_Seminar_Scheduling@mail.nih.gov with questions about this seminar.
Abstract:
Although most globular proteins fold into a single stable structure, an increasing number have been shown to remodel their secondary and tertiary structures in response to cellular stimuli. State-of-the-art algorithms predict that these fold-switching proteins adopt only one stable structure, missing their functionally critical alternative folds. Why these algorithms predict a single fold is unclear, but all of them infer protein structure from coevolved amino acid pairs. Here, we hypothesize that coevolutionary signatures are being missed. Suspecting that single-fold variants could be masking these signatures, we developed an approach, called Alternative Contact Enhancement (ACE), to search both highly diverse protein superfamilies-composed of single-fold and fold-switching variants–and protein subfamilies with more fold-switching variants. ACE successfully revealed coevolution of amino acid pairs uniquely corresponding to both conformations of 56/56 fold-switching proteins from distinct families. Then, we used ACE-derived contacts to (1) predict two experimentally consistent conformations of a candidate protein with unsolved structure and (2) develop a blind prediction pipeline for fold-switching proteins. The discovery of widespread dual-fold coevolution indicates that fold-switching sequences have been preserved by natural selection, implying that their functionalities provide evolutionary advantage and paving the way for predictions of diverse protein structures from single sequences.