NLM IRP Seminar Schedule
UPCOMING SEMINARS
RECENT SEMINARS
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July 23, 2024 Yu group
Yu Group Research Update -
July 18, 2024 Xiaofang Jiang
Jiang Lab research updates -
May 30, 2024 Deepak Gupta
Towards Answering Health-related Questions from Medical Videos: Datasets and Approaches -
May 28, 2024 Harutyun Saakyan
Simulation of protein fold evolution with atomistic details -
May 23, 2024 Leslie Ronish
Identification of fold-switching proteins by FLIM-FRET
Scheduled Seminars on Feb. 15, 2024
Contact NLM_IRP_Seminar_Scheduling@mail.nih.gov with questions about this seminar.
Abstract:
Though typically associated with a single folded state, some globular proteins remodel their secondary and/or tertiary structures in response to cellular stimuli. AlphaFold2 (AF2) readily generates one dominant protein structure for these fold-switching (a.k.a. metamorphic) proteins, but it often fails to predict their alternative experimentally observed structures. Wayment-Steele, et al. steered AF2 to predict alternative structures of a few metamorphic proteins using a method they call AF-cluster. However, their paper lacks some essential controls needed to assess AF-cluster’s reliability. We find that using ColabFold-based random sequence sampling–a method we call CF-random–is a more accurate and less computationally intense alternative to AF-cluster. In addition, CF-random effectively captures the alternative conformations of functional and membrane transport proteins with fewer predicted samples than other AF2-based enhanced sampling approaches. We suggest that CF-random predicts the alternative conformations of proteins using associative sequence homology rather than generative coevolutionary inference.