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Small structural alterations such as mutations induced by single nucleotide polymorphism can impact biological activity and pharmacological modulation. Covid-19 mutations, that affect viral replication and the susceptibility to antibody neutralization, and the action of antiviral drugs, are just one example. In this work, the intramolecular stability of mutated proteins, like Spike glycoprotein and its complexes with the human target, is evaluated through hydropathic intramolecular energy scoring originally conceived by Abraham and Kellogg based on the \u201cExtension of the fragment method to calculate amino acid zwitterion and side-chain partition coefficients\u201d by Abraham and Leo in <jats:italic>Proteins<\/jats:italic>: <jats:italic>Struct. Funct. Genet.<\/jats:italic> 1987, 2:130\u2009\u2212\u200952. HINT is proposed as a fast and reliable tool for the stability evaluation of any mutated system. This work has been written in honor of Prof. Donald J. Abraham (1936\u20132021).<\/jats:p>","DOI":"10.1007\/s10822-022-00477-y","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T09:02:48Z","timestamp":1667206968000},"page":"797-804","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["From oncoproteins to spike proteins: the evaluation of intramolecular stability using hydropathic force field"],"prefix":"10.1007","volume":"36","author":[{"given":"Federica","family":"Agosta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glen E.","family":"Kellogg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"Cozzini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,10,31]]},"reference":[{"key":"477_CR1","doi-asserted-by":"publisher","unstructured":"Anfinsen CB (1973) \u201cPrinciples that Govern the Folding of Protein Chains,\u201d Science (1979), vol.\u00a0181, no. 4096, pp.\u00a0223\u2013230, Jul. https:\/\/doi.org\/10.1126\/science.181.4096.223","DOI":"10.1126\/science.181.4096.223"},{"key":"477_CR2","doi-asserted-by":"publisher","unstructured":"Bryngelson JD, Onuchic JN, Socci ND, Wolynes PG (1995) \u201cFunnels, pathways, and the energy landscape of protein folding: A synthesis,\u201d Proteins: Structure, Function, and Genetics, vol.\u00a021, no. 3, pp.\u00a0167\u2013195, Mar. https:\/\/doi.org\/10.1002\/prot.340210302","DOI":"10.1002\/prot.340210302"},{"key":"477_CR3","doi-asserted-by":"publisher","unstructured":"Godoy-Ruiz R, Perez-Jimenez R, Ibarra-Molero B, Sanchez-Ruiz JM (Feb. 2004) Relation Between Protein Stability, Evolution and Structure, as Probed by Carboxylic Acid Mutations. 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RAS HINTscores (K-N and H isoforms) show the effect of all mutations on protein stability; S2. B-RAF HINTscores; S3. SPIKE proteins HINT score considering the trimeric conformation, the receptor-binding domain, and the RBD-ACE2 complexes.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Supporting Information"}},{"value":"The authors have no competing interests to declare.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Statements and Declaration"}}]}}