Current computer modeling cannot explain why two highly similar sequences fold into different structures.

Show simple item record Allison, Jane R Bergeler, Maike Hansen, Niels van Gunsteren, Wilfred F
dc.coverage.spatial United States 2022-05-25T04:57:52Z 2022-05-25T04:57:52Z 2011-12
dc.identifier.citation (2011). Biochemistry, 50(50), 10965-10973.
dc.identifier.issn 0006-2960
dc.description.abstract The remarkable recent creation of two proteins that fold into two completely different and stable structures, exhibit different functions, yet differ by only a few amino acids poses a conundrum to those hoping to understand how sequence encodes structure. Here, computer modeling uniquely allows the characterization of not only the native structure of each minimally different sequence but also systems in which each sequence was modeled onto the fold of the alternate sequence. The reasons for the different structural preferences of two pairs of highly similar sequences are explored by a combination of structure analyses, comparison of potential energies calculated from energy-minimized single structures and trajectories produced from molecular dynamics simulations, and application of a novel method for calculating free energy differences. The sensitivity of such analyses to the choice of force field is also explored. Many of the hypotheses proposed on the basis of the nuclear magnetic resonance model structures of the proteins with 95% identical sequences are supported. However, each level of analysis provides different predictions regarding which sequence-structure combination should be most favored, highlighting the fact that protein structure and stability result from a complex combination of interdependent factors.
dc.format.medium Print-Electronic
dc.language eng
dc.publisher American Chemical Society (ACS)
dc.relation.ispartofseries Biochemistry
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.
dc.subject Humans
dc.subject Serum Albumin
dc.subject Bacterial Proteins
dc.subject Nuclear Magnetic Resonance, Biomolecular
dc.subject Reproducibility of Results
dc.subject Protein Engineering
dc.subject Sequence Alignment
dc.subject Amino Acid Sequence
dc.subject Protein Conformation
dc.subject Protein Structure, Tertiary
dc.subject Protein Folding
dc.subject Sequence Homology, Amino Acid
dc.subject Thermodynamics
dc.subject Models, Molecular
dc.subject Databases, Protein
dc.subject Protein Stability
dc.subject Molecular Dynamics Simulation
dc.subject Serum Albumin, Human
dc.subject Bioengineering
dc.subject Biotechnology
dc.subject Generic health relevance
dc.subject 7 Affordable and Clean Energy
dc.subject Science & Technology
dc.subject Life Sciences & Biomedicine
dc.subject Biochemistry & Molecular Biology
dc.subject FORCE-FIELD
dc.subject PROTEINS
dc.subject IDENTITY
dc.subject 53A6
dc.subject 0601 Biochemistry and Cell Biology
dc.subject 0304 Medicinal and Biomolecular Chemistry
dc.subject 1101 Medical Biochemistry and Metabolomics
dc.title Current computer modeling cannot explain why two highly similar sequences fold into different structures.
dc.type Journal Article
dc.identifier.doi 10.1021/bi2015663
pubs.issue 50
pubs.begin-page 10965
pubs.volume 50 2022-04-28T03:40:12Z
dc.rights.holder Copyright: The author en
dc.identifier.pmid 22082195 (pubmed)
pubs.end-page 10973
pubs.publication-status Published
dc.rights.accessrights en
pubs.subtype Comparative Study
pubs.subtype Research Support, Non-U.S. Gov't
pubs.subtype Journal Article
pubs.elements-id 739603 Science Biological Sciences
dc.identifier.eissn 1520-4995
pubs.record-created-at-source-date 2022-04-28 2011-11-23

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