When does a funnel become a trap? A Gömböc-inspired model of protein folding landscapes
- 1Laboratory of Chemoinformatics, Infochemistry Scientific Center, ITMO University Lomonosova Street 9 Saint Petersburg 191002 Russia
- 2Department of Biology and General Genetics, Sechenov First Moscow State Medical University (Sechenov University) Izmaylovskiy Boulevard 8 Moscow 105043 Russia
- 3College of Engineering and Applied Science, University of Wisconsin-Milwaukee Milwaukee WI 53211 USA
Abstract
The protein folding problem remains a fundamental challenge in biophysics. While energy landscape theory resolves Levinthal's paradox through funnel-shaped landscapes, the quantitative effects of landscape ruggedness on folding kinetics are not fully understood. We introduce a computational model inspired by Gömböc, a convex 3D shape with one stable equilibrium and one unstable equilibrium, as an analogy for protein folding landscapes. Using a tunable ruggedness parameter, we simulate “folding” across multiple ruggedness conditions (r = 0 and r = 10−8 to 10−3), spanning five orders of magnitude in the positive-r regime. At minimal ruggedness (10−8), the model achieves 83% success in reaching native-like states. Increasing the ruggedness to 10−7–10−5 reduces the success rate to 25–39%, reflecting landscape trapping as an analog for kinetic trapping in physical folding. Benchmarking against the TPR1 domain via Rosetta and AlphaFold3 reveals native-like coverages of 77% and 90%, respectively, showing qualitative correspondence with the Gömböc model's success rates at low ruggedness. These findings suggest that the Gömböc-inspired model captures essential features of folding landscape quality and may serve as a useful heuristic for comparing foldability across different systems, bridging mathematical topology with protein biophysics.
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BibTeX
@article{shityakov2026when,
title = {{When does a funnel become a trap? A Gömböc-inspired model of protein folding landscapes}},
author = {Sergey Shityakov and Ekaterina V. Skorb and Michael Nosonovsky},
journal = {RSC Advances},
year = {2026},
month = nov,
doi = {10.1039/d6ra07903b},
url = {https://doi.org/10.1039/d6ra07903b},
note = {CC BY-NC 3.0},
}
RIS
TY - JOUR
TI - When does a funnel become a trap? A Gömböc-inspired model of protein folding landscapes
AU - Sergey Shityakov
AU - Ekaterina V. Skorb
AU - Michael Nosonovsky
PY - 2026
DA - 2026/11/04
JO - RSC Advances
DO - 10.1039/d6ra07903b
UR - https://doi.org/10.1039/d6ra07903b
AB - The protein folding problem remains a fundamental challenge in biophysics. While energy landscape theory resolves Levinthal's paradox through funnel-shaped landscapes, the quantitative effects of landscape ruggedness on folding kinetics are not fully understood. We introduce a computational model inspired by Gömböc, a convex 3D shape with one stable equilibrium and one unstable equilibrium, as an analogy for protein folding landscapes. Using a tunable ruggedness parameter, we simulate “folding” across multiple ruggedness conditions (r = 0 and r = 10−8 to 10−3), spanning five orders of magnitude in the positive-r regime. At minimal ruggedness (10−8), the model achieves 83% success in reaching native-like states. Increasing the ruggedness to 10−7–10−5 reduces the success rate to 25–39%, reflecting landscape trapping as an analog for kinetic trapping in physical folding. Benchmarking against the TPR1 domain via Rosetta and AlphaFold3 reveals native-like coverages of 77% and 90%, respectively, showing qualitative correspondence with the Gömböc model's success rates at low ruggedness. These findings suggest that the Gömböc-inspired model captures essential features of folding landscape quality and may serve as a useful heuristic for comparing foldability across different systems, bridging mathematical topology with protein biophysics.
SN - 2046-2069
ER -