ArticleBiophysical journal2016
Hidden Markov Modeling with Detailed Balance and Its Application to Single Protein Folding.
Article in Biophysical journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Single-molecule dissection of CFTR folding defects and pharmacological rescue.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Nonlinear stiffness of NompC gating spring and its implication in mechanotransduction.Science advances · 2026Article
- SNAP-25 disease variants affect synaptic transmission by destabilizing SNARE complexes within a multimeric SNARE ring.Cell reports · 2026Article
- Single-molecule tweezers decode hidden dimerization patterns of membrane proteins within lipid bilayers.Nature communications · 2025Article
- Increasing the accuracy of single-molecule data analysis using tMAVEN.Biophysical journal · 2024Article
- Single-Molecule Imaging of Integral Membrane Protein Dynamics and Function.Annual review of biophysics · 2024Review
- Single-molecule magnetic tweezers to probe the equilibrium dynamics of individual proteins at physiologically relevant forces and timescales.Nature protocols · 2024Review
- Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes.Nature communications · 2024Article
- Increasing the accuracy of single-molecule data analysis using tMAVEN.bioRxiv : the preprint server for biology · 2024Article
- Robust membrane protein tweezers reveal the folding speed limit of helical membrane proteins.eLife · 2023Article
- Learning continuous potentials from smFRET.Biophysical journal · 2023Article
- A dynamic template complex mediates Munc18-chaperoned SNARE assembly.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Energetics, kinetics, and pathways of SNARE assembly in membrane fusion.Critical reviews in biochemistry and molecular biology · 2022Review
- Polybasic Patches in Both C2 Domains of Synaptotagmin-1 Are Required for Evoked Neurotransmitter Release.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Mechanical regulation of talin through binding and history-dependent unfolding.Science advances · 2022Article
- Evolutionary balance between foldability and functionality of a glucose transporter.Nature chemical biology · 2022Article
- Stepwise membrane binding of extended synaptotagmins revealed by optical tweezers.Nature chemical biology · 2022Article
- Quantitative Models of Lipid Transfer and Membrane Contact Formation.Contact (Thousand Oaks (Ventura County, Calif.)) · 2022Article
- Single-molecule manipulation of macromolecules on GUV or SUV membranes using optical tweezers.Biophysical journal · 2021Article
- Generalizing HMMs to Continuous Time for Fast Kinetics: Hidden Markov Jump Processes.Biophysical journal · 2021Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Hidden Markov modeling (HMM) has revolutionized kinetic studies of macromolecules. However, results from HMM often violate detailed balance when applied to the transitions under thermodynamic equilibrium, and the consequence of such violation has not been well understood. Here, to our knowledge, we developed a new HMM method that satisfies detailed balance (HMM-DB) and optimizes model parameters by gradient search. We used free energy of stable and transition states as independent fitting parameters and considered both normal and skew normal distributions of the measurement noise. We validated our method by analyzing simulated extension trajectories that mimicked experimental data of single protein folding from optical tweezers. We then applied HMM-DB to elucidate kinetics of regulated SNARE zippering containing degenerate states. For both simulated and measured trajectories, we found that HMM-DB significantly reduced overfitting of short trajectories compared to the standard HMM based on an expectation-maximization algorithm, leading to more accurate and reliable model fitting by HMM-DB. We revealed how HMM-DB could be conveniently used to derive a simplified energy landscape of protein folding. Finally, we extended HMM-DB to correct the baseline drift in single-molecule trajectories. Together, we demonstrated an efficient, versatile, and reliable method of HMM for kinetics studies of macromolecules under thermodynamic equilibrium.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.