All-Atom Ab Initio Folding of a Diverse Set of Proteins
Open accessAbstract
Natural proteins fold to a unique, thermodynamically dominant state. Modeling of the folding process and prediction of the native fold of proteins are two major unsolved problems in biophysics. Here, we show successful all-atom ab initio folding of a representative diverse set of proteins by using a minimalist transferable-energy model that consists of two-body atom-atom interactions, hydrogen bonding, and a local sequence-energy term that models sequence-specific chain stiffness. Starting from a random coil, the native-like structure was observed during replica exchange Monte Carlo (REMC) simulation for most proteins regardless of their structural classes; the lowest energy structure was close to native-in the range of 2-6 A root-mean-square deviation (rmsd). Our results demonstrate that the successful folding of a protein chain to its native state is governed by only a few crucial energetic terms.
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The small 5-10 kcal/mol difference in stability between native and denatured states compounded the challenge for protein structure prediction methods.
“The small (5–10 kcal/mol) difference in the stability of the native structures as compared to the denatured states151 compounded the challenge that predicting methods faced.”
From AlphaFold, Artificial Intelligence (AI), and Allostery (2022) · cites this paper as [151]
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AlphaFold, Artificial Intelligence (AI), and Allostery
Nussinov, R., Zhang, M., Liu, Y., & Jang, H. (2022) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.2c04346 · Cited by 190 · see citing works
- Authors
- Yang, J. S., Chen, W. W., Skolnick, J., & Shakhnovich, E. I.
- Affiliations
- Harvard University (US)
- University at Buffalo, State University of New York (US)
- Corresponding author
- Shakhnovich, Eugene I.
- Venue
- Structure
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 15
- Issue
- 1
- Pages
- 53-63
- ISSN
- 0969-2126 (ISSN-L)
- OpenAlex
- W1990700294
- Cited by
- 86
- References
- 42
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 7 · 2012: 4
- FWCI
- 5.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Structure (publishedVersion)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- arXiv (Cornell University)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- protein folding, hydrogen bonding, parallel tempering, native structure prediction, random coil
- MeSH terms
- Models, Molecular, Monte Carlo Method, Protein Structure, Secondary, Protein Folding
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