Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Computational protein design is a challenge for implicit solvation models.

Alfonso Jaramillo1, Shoshana J Wodak

  • 1Service de Conformation de Macromolécules Biologiques et Bioinformatique, CP263 Université Libre de Bruxelles, Brussels, Belgium.

Biophysical Journal
|September 21, 2004
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Monoallelic POLR3A Variants Cause Early-Onset Peripheral Neuropathy.

Annals of neurology·2026
Same author

Biomolecular Interaction Prediction in the Pre- and Post-AlphaFold Era: The 8th CAPRI Evaluation.

Proteins·2025
Same author

High-yield bioproduction of virus-free virus-like P4-EKORhE multi-lysin transducing particles as an antimicrobial gene therapeutic.

Frontiers in cellular and infection microbiology·2025
Same author

Outlook on Synthetic Biology-Driven Hydrogen Production: Lessons from Algal Photosynthesis Applied to Cyanobacteria.

Energy & fuels : an American Chemical Society journal·2025
Same author

CAPRI-Q: The CAPRI resource evaluating the quality of predicted structures of protein complexes.

Journal of molecular biology·2024
Same author

T7 phage-assisted evolution of riboswitches using error-prone replication and dual selection.

Scientific reports·2024
Same journal

Heterogeneous binding of SARS-CoV2 fusion peptide on complex cellular membranes enhances its fusogenicity.

Biophysical journal·2026
Same journal

Tau protein differentially affects Piezo1 and Kir2.1 channels in brain capillary endothelial cells.

Biophysical journal·2026
Same journal

Emergent Intercellular Junction Stability during Cyclic Tissue Loading.

Biophysical journal·2026
Same journal

Enhanced-Sampling Simulations Reveal Distinct Intermediates in SARS-CoV-2 FSE Pseudoknot Interconversion.

Biophysical journal·2026
Same journal

Structure-based simulations of the full Flock House virus capsid reveal pathways and energetics of an infection-critical peptide externalization event.

Biophysical journal·2026
Same journal

Quantifying the Peripheral Surface Information Entropy from Conformational Ensembles of Globular Protein-Peptide Complexes.

Biophysical journal·2026
See all related articles

Implicit solvation models used in computational biology often fail protein design tasks. These models inaccurately predict the energetic cost of burying amino acids, hindering accurate protein sequence selection for stable structures.

Area of Science:

  • Computational biology
  • Biophysics
  • Protein design

Background:

  • Implicit solvation models accelerate macromolecular calculations.
  • These models are assumed to accurately represent solvation effects.
  • Their performance in demanding applications like protein design is not fully understood.

Purpose of the Study:

  • To evaluate the accuracy of five implicit solvation models in protein design scenarios.
  • To assess the models' ability to predict the energetic cost of amino acid burial.
  • To determine if these models can distinguish native protein folds from non-native decoys.

Main Methods:

  • Tested five implicit solvation models: one surface area-based, two generalized Born approximations, and finite difference Poisson-Boltzmann.

Related Experiment Videos

  • Evaluated amino acid burial energies in thousands of environments from native structures and decoys.
  • Performed actual protein sequence design calculations.

    • Main Results:

    • Most models incorrectly favor burying polar over nonpolar amino acids in protein interiors.
    • This bias leads to poor performance in protein design.
    • Three models could still differentiate native folds from non-native alternatives.

    Conclusions:

    • Protein design is a stringent test for implicit solvation models, requiring precise residue solvation energy estimates.
    • Current implicit solvation models may not be sufficiently accurate for de novo protein design.
    • Distinguishing native from non-native structures is less demanding than accurate protein design.