ArticlePloS one2013
Alternative computational protocols for supercharging protein surfaces for reversible unfolding and retention of stability.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 112 citations in OpenAlex.
- Rationally engineered cationic ferritin nanoparticles overcome pre-existing immunity to adenoviral vectors.Journal of nanobiotechnology · 2026Article
- Hybrid Supercharged Antibodies: A Rational Approach to Boost Immunoassay Sensitivity via Controlled Nanoparticle Adsorption.Langmuir : the ACS journal of surfaces and colloids · 2026Article
- There is an "I" in team: individual improvements in supercharged cellulase cocktail facilitates cooperative cellulose degradation.Biotechnology for biofuels and bioproducts · 2026Article
- Development of a highly active engineered PETase enzyme for polyester degradation.The FEBS journal · 2026Article
- Site-Directed Mutagenesis Increased the Catalytic Activity and Stability ofInternational journal of molecular sciences · 2025Article
- Patulin Detoxification by Evolutionarily Divergent Reductases ofJournal of agricultural and food chemistry · 2025Article
- Design of Cell-Penetrating Domain Antibodies via a Genetically Encoded β-Lactam Amino Acid.Angewandte Chemie (International ed. in English) · 2025Article
- Form Equals Function: Influence of Coacervate Architecture on Drug Delivery Applications.ACS biomaterials science & engineering · 2024Review
- Supercharged fluorescent proteins detect lanthanides via direct antennae signaling.Nature communications · 2024Article
- PySupercharge: a python algorithm for enabling ABC transporter bacterial secretion of all proteins through amino acid mutation.Microbial cell factories · 2024Article
- Emerging Landscape of Supercharged Proteins and Peptides for Drug Delivery.ACS pharmacology & translational science · 2024Review
- Supercharged Phosphotriesterase for improved Paraoxon activity.Protein engineering, design & selection : PEDS · 2024Article
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- Tailoring FPOX enzymes for enhanced stability and expanded substrate recognition.Scientific reports · 2023Article
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- Fitness Landscape-Guided Engineering of Locally Supercharged Virus-like Particles with Enhanced Cell Uptake Properties.ACS chemical biology · 2022Article
- Protein Design: From the Aspect of Water Solubility and Stability.Chemical reviews · 2022Review
- Understanding Supramolecular Assembly of Supercharged Proteins.ACS central science · 2022Article
- Generalized Approach towards Secretion-Based Protein Production via Neutralization of Secretion-Preventing Cationic Substrate Residues.International journal of molecular sciences · 2022Article
- Spontaneous Orthogonal Protein Crosslinking via a Genetically Encoded 2-Carboxy-4-Aryl-1,2,3-Triazole.Angewandte Chemie (International ed. in English) · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Reengineering protein surfaces to exhibit high net charge, referred to as "supercharging", can improve reversibility of unfolding by preventing aggregation of partially unfolded states. Incorporation of charged side chains should be optimized while considering structural and energetic consequences, as numerous mutations and accumulation of like-charges can also destabilize the native state. A previously demonstrated approach deterministically mutates flexible polar residues (amino acids DERKNQ) with the fewest average neighboring atoms per side chain atom (AvNAPSA). Our approach uses Rosetta-based energy calculations to choose the surface mutations. Both protocols are available for use through the ROSIE web server. The automated Rosetta and AvNAPSA approaches for supercharging choose dissimilar mutations, raising an interesting division in surface charging strategy. Rosetta-supercharged variants of GFP (RscG) ranging from -11 to -61 and +7 to +58 were experimentally tested, and for comparison, we re-tested the previously developed AvNAPSA-supercharged variants of GFP (AscG) with +36 and -30 net charge. Mid-charge variants demonstrated ∼3-fold improvement in refolding with retention of stability. However, as we pushed to higher net charges, expression and soluble yield decreased, indicating that net charge or mutational load may be limiting factors. Interestingly, the two different approaches resulted in GFP variants with similar refolding properties. Our results show that there are multiple sets of residues that can be mutated to successfully supercharge a protein, and combining alternative supercharge protocols with experimental testing can be an effective approach for charge-based improvement to refolding.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.