ArticleMolecular pharmaceutics2014
Lysine and arginine content of proteins: computational analysis suggests a new tool for solubility design.
Article in Molecular pharmaceutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- Structural Features of a Tiny Viral Protein, ORF7b of SARS-CoV-2.International journal of molecular sciences · 2026Article
- Structure-Guided Design and in Vivo Validation of a VP4-Derived Subunit Vaccine Candidate against Bovine Rotavirus.Molecular biotechnology · 2026Article
- Computational optimization of DEK1 calpain domain solubility through integrated structural modelling and data-driven targeted mutagenesis.Scientific reports · 2026Article
- Strategies for enhancing protein solubility: methods, applications, and prospects.NPJ science of food · 2026Review
- PInteract: Detecting Aromatic-Involving Motifs in Proteins and Protein-Nucleic Acid Complexes.Biomolecules · 2025Article
- SOuLMuSiC, a novel tool for predicting the impact of mutations on protein solubility.Scientific reports · 2025Article
- X-ray crystallographic and hydrogen deuterium exchange studies confirm alternate kinetic models for homolog insulin monomers.PloS one · 2025Article
- Increased preference for lysine over arginine in spike proteins of SARS-CoV-2 BA.2.86 variant and its daughter lineages.PloS one · 2025Article
- Targeting Efficient Features of Urate Oxidase to Increase Its Solubility.Applied biochemistry and biotechnology · 2024Article
- Understanding the Specific Implications of Amino Acids in the Antibody Development.The protein journal · 2024Review
- Effects of Charge Sequence Pattern and Lysine-to-Arginine Substitution on the Structural Stability of Bioinspired Polyampholytes.Biomacromolecules · 2024Article
- Computational investigation of missense somatic mutations in cancer and potential links to pH-dependence and proteostasis.PloS one · 2024Article
- Photo-caged 2-butene-1,4-dial as an efficient, target-specific photo-crosslinker for covalent trapping of DNA-binding proteins.Chemical science · 2023Article
- Nonspecific Binding of Adenosine Tripolyphosphate and Tripolyphosphate Modulates the Phase Behavior of Lysozyme.Journal of the American Chemical Society · 2023Article
- Analysis of copper-induced protein precipitation across the E. coli proteome.Metallomics : integrated biometal science · 2023Article
- Role of Nitric Oxide-Derived Metabolites in Reactions of Methylglyoxal with Lysine and Lysine-Rich Protein Leghemoglobin.International journal of molecular sciences · 2022Article
- Chemical Conjugation to Less Targeted Proteinogenic Amino Acids.Chembiochem : a European journal of chemical biology · 2022Review
- Protein Design: From the Aspect of Water Solubility and Stability.Chemical reviews · 2022Review
- Computational design and experimental characterisation of a stable human heparanase variant.RSC chemical biology · 2022Article
- Rational design of a new variant of Reteplase with optimized physicochemical profile and large-scale production in Escherichia coli.World journal of microbiology & biotechnology · 2022Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prediction and engineering of protein solubility is an important but imprecise area. While some features are routinely used, such as the avoidance of extensive non-polar surface area, scope remains for benchmarking of sequence and structural features with experimental data. We study properties in the context of experimental solubilities, protein gene expression levels, and families of abundant proteins (serum albumin and myoglobin) and their less abundant paralogues. A common feature that emerges for proteins with elevated solubility and at higher expression and abundance levels is an increased ratio of lysine content to arginine content. We suggest that the same properties of arginine that give rise to its recorded propensity for specific interaction surfaces also lead to favorable interactions at nonspecific contacts, and thus lysine is favored for proteins at relatively high concentration. A survey of protein therapeutics shows that a significant subset possesses a relatively low lysine to arginine ratio, and therefore may not be favored for high protein concentration. We conclude that modulation of lysine and arginine content could prove a useful and relatively simple addition to the toolkit available for engineering protein solubility in biotechnological applications.
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