d‑Retro Inverso Amylin and the Stability of Amylin Fibrils
Motivated by the role that amylin aggregates play in type-II diabetes, we compare the stability of regular amylin fibrils with the stability of fibrils where l-amino acid chains are replaced by d-retro inverso (DRI) amylin, that is, peptides where the sequence of amino acids is reversed, and at the...
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| Veröffentlicht in: | Journal of chemical theory and computation 2020-08, Vol.16 (8), p.5358-5368 |
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| creator | Pandey, Preeti Nguyen, Natalie Hansmann, Ulrich H.E |
| description | Motivated by the role that amylin aggregates play in type-II diabetes, we compare the stability of regular amylin fibrils with the stability of fibrils where l-amino acid chains are replaced by d-retro inverso (DRI) amylin, that is, peptides where the sequence of amino acids is reversed, and at the same time, the l-amino acids are replaced by their mirror images. Our molecular dynamics simulations show that despite leading to only a marginal difference in the fibril structure and stability, aggregating DRI-amylin peptides have different patterns of contacts and hydrogen bonding. Because of these differences, DRI-amylin, when interacting with regular (l) amylin, alters the elongation process and lowers the stability of hybrid amylin fibrils. Our results not only suggest the potential use of DRI-amylin as an inhibitor of amylin fibril formation but also point to the possibility of using the insertion of DRI proteins in l-assemblies as a way to probe the role of certain kinds of hydrogen bonds in supramolecular assemblies or aggregates. |
| doi_str_mv | 10.1021/acs.jctc.0c00523 |
| format | Article |
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Our molecular dynamics simulations show that despite leading to only a marginal difference in the fibril structure and stability, aggregating DRI-amylin peptides have different patterns of contacts and hydrogen bonding. Because of these differences, DRI-amylin, when interacting with regular (l) amylin, alters the elongation process and lowers the stability of hybrid amylin fibrils. 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Chem. Theory Comput</addtitle><description>Motivated by the role that amylin aggregates play in type-II diabetes, we compare the stability of regular amylin fibrils with the stability of fibrils where l-amino acid chains are replaced by d-retro inverso (DRI) amylin, that is, peptides where the sequence of amino acids is reversed, and at the same time, the l-amino acids are replaced by their mirror images. Our molecular dynamics simulations show that despite leading to only a marginal difference in the fibril structure and stability, aggregating DRI-amylin peptides have different patterns of contacts and hydrogen bonding. Because of these differences, DRI-amylin, when interacting with regular (l) amylin, alters the elongation process and lowers the stability of hybrid amylin fibrils. Our results not only suggest the potential use of DRI-amylin as an inhibitor of amylin fibril formation but also point to the possibility of using the insertion of DRI proteins in l-assemblies as a way to probe the role of certain kinds of hydrogen bonds in supramolecular assemblies or aggregates.</description><subject>Aggregates</subject><subject>Amino acids</subject><subject>Assemblies</subject><subject>Biomolecular Systems</subject><subject>Elongation</subject><subject>Humans</subject><subject>Hydrogen bonding</subject><subject>Hydrogen bonds</subject><subject>Islet Amyloid Polypeptide - chemistry</subject><subject>Molecular dynamics</subject><subject>Molecular Dynamics Simulation</subject><subject>Peptides</subject><subject>Protein Stability</subject><subject>Structural stability</subject><issn>1549-9618</issn><issn>1549-9626</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctKxDAUhoMoXkb3rqTgxoUdc2vSggiDeBkQBC_rkKaJZmgbTdqB2fkKvqJPYnQuqODZ5MD5_v_k8AOwj-AQQYxOpArDierUECoIM0zWwDbKaJEWDLP1VY_yLbATwgRCQigmm2CLYMY4z-k2OK0-3t7vdOddMm6n2geXjJpZbdtEtlXSPevkvpOlrW03S5xZzi5t6W0ddsGGkXXQe4t3AB4vLx7Or9Ob26vx-egmlZShLiWaEVJVGSkpLiXBWKIKKqoNLSRCMOM5RLwy2qjMIMMhL0ysnFPIOOMyIwNwNvd96ctGV0q3nZe1ePG2kX4mnLTi96S1z-LJTQWnuMAZjwZHCwPvXnsdOtHYoHRdy1a7PghMMaUUowJH9PAPOnG9b-N5kSKMElTkLFJwTinvQvDarD6DoPiKRsRoxFc0YhFNlBz8PGIlWGYRgeM58C1dLv3X7xN_M5q5</recordid><startdate>20200811</startdate><enddate>20200811</enddate><creator>Pandey, Preeti</creator><creator>Nguyen, Natalie</creator><creator>Hansmann, Ulrich H.E</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SC</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>JQ2</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-0700-4835</orcidid></search><sort><creationdate>20200811</creationdate><title>d‑Retro Inverso Amylin and the Stability of Amylin Fibrils</title><author>Pandey, Preeti ; Nguyen, Natalie ; Hansmann, Ulrich H.E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a461t-3e633dd53b42ba322a1d0c4ef49a110578017dfefc5f1f7079ffff87406767a53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Aggregates</topic><topic>Amino acids</topic><topic>Assemblies</topic><topic>Biomolecular Systems</topic><topic>Elongation</topic><topic>Humans</topic><topic>Hydrogen bonding</topic><topic>Hydrogen bonds</topic><topic>Islet Amyloid Polypeptide - chemistry</topic><topic>Molecular dynamics</topic><topic>Molecular Dynamics Simulation</topic><topic>Peptides</topic><topic>Protein Stability</topic><topic>Structural stability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pandey, Preeti</creatorcontrib><creatorcontrib>Nguyen, Natalie</creatorcontrib><creatorcontrib>Hansmann, Ulrich H.E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Computer and Information Systems Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of chemical theory and computation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pandey, Preeti</au><au>Nguyen, Natalie</au><au>Hansmann, Ulrich H.E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>d‑Retro Inverso Amylin and the Stability of Amylin Fibrils</atitle><jtitle>Journal of chemical theory and computation</jtitle><addtitle>J. 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| source | MEDLINE; ACS Publications |
| subjects | Aggregates Amino acids Assemblies Biomolecular Systems Elongation Humans Hydrogen bonding Hydrogen bonds Islet Amyloid Polypeptide - chemistry Molecular dynamics Molecular Dynamics Simulation Peptides Protein Stability Structural stability |
| title | d‑Retro Inverso Amylin and the Stability of Amylin Fibrils |
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