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 Concept Videos

Conserved Binding Sites01:49

Conserved Binding Sites

4.3K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.3K
Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

11.2K
Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
11.2K
Protein Folding01:22

Protein Folding

120.0K
Overview
120.0K
Point and Frameshift Mutations01:30

Point and Frameshift Mutations

71
Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
71
Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

3.8K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.8K
Mutations01:39

Mutations

84.2K
Overview
84.2K

You might also read

Related Articles

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

Sort by
Same author

Prognostic value of gross tumour volume in laryngeal cancer: a systematic review and meta-analysis.

The Journal of laryngology and otology·2026
Same author

TransKla: A Local-Global Cross-Attention Based Transformer Approach for Prediction of Lysine Lactylation Sites.

Journal of chemical information and modeling·2026
Same author

Enhanced electrochemical performance of eco-friendly Cr-doped ZnO/RGO nanocomposites for pioneering supercapacitor applications.

Frontiers in chemistry·2026
Same author

Latent fingerprint development ability of spinel copper aluminate (CuAl<sub>2</sub>O<sub>4</sub>) nanoparticles.

Frontiers in chemistry·2026
Same author

The recent progress in the catalytic conversion of nitroarene into amino arene catalyzed by heterogeneous metal based nano catalyst.

Frontiers in chemistry·2026
Same author

Corrigendum to "evaluation of laser-induced breakdown spectroscopy for nutritional and trace elemental mapping in Otostegia limbata medicinal plant" [Spectrochim. Acta part A: Mol. Biomol. Spectrosc. 344 (2026) 126645].

Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy·2026
Same journal

Mapping Evolution of Molecules across Biochemistry with Assembly Theory.

Journal of chemical information and modeling·2026
Same journal

Structural Proteomics-Based Deciphering of Hydrophobic Packing Fingerprints Informing Protein Thermostability in TIM Barrels.

Journal of chemical information and modeling·2026
Same journal

Bridging between Structure-Based and Data-Driven Affinity Prediction.

Journal of chemical information and modeling·2026
Same journal

Reinforcement Learning-Driven Multiproperty Optimization in Molecular Design Using Multicontext Transcriptome Data.

Journal of chemical information and modeling·2026
Same journal

EnsembleCycPerm: Interpretable Modeling of Cyclic Peptide Permeability through Solvent-Dependent Conformational Ensembles.

Journal of chemical information and modeling·2026
Same journal

Resolving Conformational Preferences of Monosaccharides from <sup>1</sup>H and <sup>13</sup>C NMR Chemical Shifts Using an Integrated MD and QM Approach.

Journal of chemical information and modeling·2026
See all related articles

Related Experiment Video

Updated: Sep 1, 2025

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
08:04

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Published on: June 6, 2025

445

PROST: AlphaFold2-aware Sequence-Based Predictor to Estimate Protein Stability Changes upon Missense Mutations.

Shahid Iqbal1,2,3, Fang Ge4, Fuyi Li2,3

  • 1Department of Data Science and AI, Faculty of IT, Monash University, Clayton, Victoria 3800, Australia.

Journal of Chemical Information and Modeling
|August 16, 2022
PubMed
Summary
This summary is machine-generated.

We developed PROST, a new sequence-based predictor for protein stability changes caused by missense mutations. PROST accurately models these changes, outperforming existing methods, especially when structural information is unavailable.

More Related Videos

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
06:50

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

2.0K
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

10.7K

Related Experiment Videos

Last Updated: Sep 1, 2025

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
08:04

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Published on: June 6, 2025

445
Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
06:50

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

2.0K
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

10.7K

Area of Science:

  • Biochemistry and Molecular Biology
  • Computational Biology
  • Bioinformatics

Background:

  • Accurate prediction of protein stability changes is crucial for protein engineering and understanding missense mutations in diseases.
  • Existing sequence-based predictors have limitations in accurately modeling these stability changes.

Purpose of the Study:

  • To develop a novel, highly accurate sequence-based predictor, PROST (protein stability), for estimating changes in protein stability (Gibbs' free energy change, ΔΔG) upon single-point missense mutations.
  • To integrate diverse sequence and predicted structural features for improved prediction accuracy.

Main Methods:

  • PROST utilizes a weighted average ensemble model combining extreme gradient boosting (XGBoost) and extra-trees regressors.
  • It extracts a comprehensive set of descriptors including sequence-based features, physicochemical properties, evolutionary information, and predicted structural features from various sources.
  • The model is trained on a large dataset of direct and hypothetical reverse mutations (S5294) and optimized using grid search with 5-fold cross-validation.

Main Results:

  • PROST demonstrates superior performance in blinded tests across nine diverse datasets (frataxin, S217, S349, Ssym, S669, Myoglobin, CAGI5, p53, S276), outperforming state-of-the-art sequence-based and structure-based predictors.
  • A case study on frataxin protein mutation scanning highlights PROST's practical utility.
  • PROST consistently outperforms other leading predictors like BoostDDG, SAAFEC-SEQ, ACDC-NN-seq, and DDGun.

Conclusions:

  • PROST is a robust and accurate sequence-based predictor for modeling protein stability changes due to missense mutations.
  • It offers a valuable tool for protein engineering and disease mutation analysis, particularly when protein structural information is inaccessible.
  • The source code and models are publicly available for broader research application.