DOI: 10.1073/pnas.042496899. α-Helical stabilization by side chain shielding of backbone hydrogen bonds

α-Helical stabilization by side chain shielding of backbone hydrogen bonds

10.1073/pnas.042496899

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

We study atomic models of the thermodynamics of the structural transition of peptides that form α-helices. The effect of sequence variation on α-helix formation for alanine-rich peptides, Ac-Ala 21 - methyl amide (A21) and Ac-A 5 (AAARA) 3 A-methyl amide (Fs peptide), is investigated by atomic simulation studies of the thermodynamics of the helix-coil transition in explicit water. The simulations show that the guanidinium group in the Arg side chains in the Fs peptide interacts with the carbonyl group four amino acids upstream in the chain and desolvates backbone hydrogen bonds. This desolvation can be directly correlated with a higher probability of hydrogen bond formation. We find that Fs has higher helical content than A21 at all temperatures. A small modification in the amber force field reproduces the experimental helical content and helix-coil transition temperatures for the Fs peptide.

Bibliography

GarcÃa, A. E., & Sanbonmatsu, K. Y. (2002). Î±-Helical stabilization by side chain shielding of backbone hydrogen bonds. Proceedings of the National Academy of Sciences, 99(5), 2782â2787.

Authors 2

Angel E. García (first)
Kevin Y. Sanbonmatsu (additional)

References 47 Referenced 418

10.1063/1.881414
10.1002/bip.1968.360060308
10.1021/ma60026a016
10.1073/pnas.84.24.8898
10.1126/science.2237416
10.1146/annurev.bb.21.060192.000523
10.1002/pro.5560030514
10.1021/ja990056x
10.1021/ja982319d
10.1063/1.1731802
10.1021/j100189a015
10.1063/1.1730390
H A Scheraga Perspectives in Structural Biology, eds M Vijayan, N Yathindra, A Kolaskar (Indian Acad. Sci., Bangalore), pp. 275–292 (1999). / Perspectives in Structural Biology by Scheraga H A (1999)
10.1073/pnas.240455797
10.1021/ja9801947
10.1073/pnas.200343197
10.1073/pnas.96.9.4930
10.1016/0022-2836(92)90229-D
Soman K. Karimi A. & Case D. Biopolymers 31 1351–1361. (10.1002/bip.360311202)
10.1016/0022-2836(92)90264-K
10.1021/bi00238a032
10.1021/bi00238a033
10.1021/ja00076a089
10.1006/jmbi.1997.1246
10.1021/jp952674f
10.1103/PhysRevLett.85.2637
10.1002/1097-0134(20010101)42:1<77::AID-PROT80>3.0.CO;2-#
10.1002/(SICI)1097-0134(19990215)34:3<269::AID-PROT1>3.0.CO;2-3
10.1006/jmbi.1998.1885
10.1021/bi952217p
10.1126/science.1502559
10.1126/science.8469972
10.1021/bi9704764
10.1021/ja003381p
10.1063/1.445869
10.1016/S0009-2614(99)01123-9
10.1002/1097-0134(20010215)42:3<345::AID-PROT50>3.0.CO;2-H
10.1126/science.2734612
10.1021/ja00124a002
D Pearlman, D A Case, J W Caldwell, W S Ross, I T E Cheatam, D M Ferguson, U C Singh, P Weiner, P Kollman amber 4.1., 1995). / amber 4.1. by Pearlman D (1995)
10.1016/0301-4622(94)00057-3
10.1088/0953-8984/6/23A/018
10.1063/1.448118
10.1038/nsb0694-399
10.1021/ja962310g
10.1110/ps.8.6.1292
P A Kollman, R W Dixon, W D Cornell, T Fox, C Chipot, A Pohorille Computer Simulations of Biological Systems, ed W van Gunsteren (ESCOM, Dordrecht, The Netherlands, 1997). / Computer Simulations of Biological Systems by Kollman P A (1997)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:37 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 9:59 a.m.)
Indexed	6 days, 9 hours ago (Aug. 30, 2025, 1:17 p.m.)
Issued	23 years, 6 months ago (Feb. 26, 2002)
Published	23 years, 6 months ago (Feb. 26, 2002)
Published Online	23 years, 6 months ago (Feb. 26, 2002)
Published Print	23 years, 6 months ago (March 5, 2002)

Funders 0

None

BibTeX

@article{Garc_a_2002, title={α-Helical stabilization by side chain shielding of backbone hydrogen bonds}, volume={99}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.042496899}, DOI={10.1073/pnas.042496899}, number={5}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={García, Angel E. and Sanbonmatsu, Kevin Y.}, year={2002}, month=feb, pages={2782–2787} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        30
      ]
    ],
    "date-time": "2025-08-30T17:17:15Z",
    "timestamp": 1756574235451
  },
  "reference-count": 47,
  "publisher": "Proceedings of the National Academy of Sciences",
  "issue": "5",
  "content-domain": {
    "domain": [
      "www.pnas.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2002,
        3,
        5
      ]
    ]
  },
  "abstract": "<jats:p>\n            We study atomic models of the thermodynamics of the structural transition of peptides that form \u03b1-helices. The effect of sequence variation on \u03b1-helix formation for alanine-rich peptides, Ac-Ala\n            <jats:sub>21</jats:sub>\n            - methyl amide (A21) and Ac-A\n            <jats:sub>5</jats:sub>\n            (AAARA)\n            <jats:sub>3</jats:sub>\n            A-methyl amide (Fs peptide), is investigated by atomic simulation studies of the thermodynamics of the helix-coil transition in explicit water. The simulations show that the guanidinium group in the Arg side chains in the Fs peptide interacts with the carbonyl group four amino acids upstream in the chain and desolvates backbone hydrogen bonds. This desolvation can be directly correlated with a higher probability of hydrogen bond formation. We find that Fs has higher helical content than A21 at all temperatures. A small modification in the\n            <jats:sc>amber</jats:sc>\n            force field reproduces the experimental helical content and helix-coil transition temperatures for the Fs peptide.\n          </jats:p>",
  "DOI": "10.1073/pnas.042496899",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T14:37:36Z",
    "timestamp": 1027694256000
  },
  "page": "2782-2787",
  "update-policy": "http://dx.doi.org/10.1073/pnas.cm10313",
  "source": "Crossref",
  "is-referenced-by-count": 418,
  "title": "\u03b1-Helical stabilization by side chain shielding of backbone hydrogen bonds",
  "prefix": "10.1073",
  "volume": "99",
  "author": [
    {
      "given": "Angel E.",
      "family": "Garc\u00eda",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Theoretical Division, T10 MS K710, Los Alamos National Laboratory, Los Alamos, NM 87545"
        }
      ]
    },
    {
      "given": "Kevin Y.",
      "family": "Sanbonmatsu",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Theoretical Division, T10 MS K710, Los Alamos National Laboratory, Los Alamos, NM 87545"
        }
      ]
    }
  ],
  "member": "341",
  "published-online": {
    "date-parts": [
      [
        2002,
        2,
        26
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_3_3_1_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1063/1.881414"
    },
    {
      "key": "e_1_3_3_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/bip.1968.360060308"
    },
    {
      "key": "e_1_3_3_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ma60026a016"
    },
    {
      "key": "e_1_3_3_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.84.24.8898"
    },
    {
      "key": "e_1_3_3_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2237416"
    },
    {
      "key": "e_1_3_3_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.bb.21.060192.000523"
    },
    {
      "key": "e_1_3_3_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/pro.5560030514"
    },
    {
      "key": "e_1_3_3_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja990056x"
    },
    {
      "key": "e_1_3_3_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja982319d"
    },
    {
      "key": "e_1_3_3_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1063/1.1731802"
    },
    {
      "key": "e_1_3_3_11_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/j100189a015"
    },
    {
      "key": "e_1_3_3_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1063/1.1730390"
    },
    {
      "key": "e_1_3_3_13_2",
      "first-page": "275",
      "volume-title": "Perspectives in Structural Biology",
      "author": "Scheraga H A",
      "year": "1999",
      "unstructured": "H A Scheraga Perspectives in Structural Biology, eds M Vijayan, N Yathindra, A Kolaskar (Indian Acad. Sci., Bangalore), pp. 275\u2013292 (1999)."
    },
    {
      "key": "e_1_3_3_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.240455797"
    },
    {
      "key": "e_1_3_3_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja9801947"
    },
    {
      "key": "e_1_3_3_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.200343197"
    },
    {
      "key": "e_1_3_3_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.96.9.4930"
    },
    {
      "key": "e_1_3_3_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0022-2836(92)90229-D"
    },
    {
      "key": "e_1_3_3_19_2",
      "doi-asserted-by": "crossref",
      "unstructured": "Soman K. Karimi A. & Case D. Biopolymers 31 1351\u20131361.",
      "DOI": "10.1002/bip.360311202"
    },
    {
      "key": "e_1_3_3_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0022-2836(92)90264-K"
    },
    {
      "key": "e_1_3_3_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00238a032"
    },
    {
      "key": "e_1_3_3_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00238a033"
    },
    {
      "key": "e_1_3_3_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00076a089"
    },
    {
      "key": "e_1_3_3_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/jmbi.1997.1246"
    },
    {
      "key": "e_1_3_3_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp952674f"
    },
    {
      "key": "e_1_3_3_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1103/PhysRevLett.85.2637"
    },
    {
      "key": "e_1_3_3_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/1097-0134(20010101)42:1<77::AID-PROT80>3.0.CO;2-#"
    },
    {
      "key": "e_1_3_3_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/(SICI)1097-0134(19990215)34:3<269::AID-PROT1>3.0.CO;2-3"
    },
    {
      "key": "e_1_3_3_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/jmbi.1998.1885"
    },
    {
      "key": "e_1_3_3_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi952217p"
    },
    {
      "key": "e_1_3_3_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1502559"
    },
    {
      "key": "e_1_3_3_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.8469972"
    },
    {
      "key": "e_1_3_3_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi9704764"
    },
    {
      "key": "e_1_3_3_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja003381p"
    },
    {
      "key": "e_1_3_3_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1063/1.445869"
    },
    {
      "key": "e_1_3_3_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0009-2614(99)01123-9"
    },
    {
      "key": "e_1_3_3_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/1097-0134(20010215)42:3<345::AID-PROT50>3.0.CO;2-H"
    },
    {
      "key": "e_1_3_3_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2734612"
    },
    {
      "key": "e_1_3_3_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00124a002"
    },
    {
      "key": "e_1_3_3_40_2",
      "volume-title": "amber 4.1.",
      "author": "Pearlman D",
      "year": "1995",
      "unstructured": "D Pearlman, D A Case, J W Caldwell, W S Ross, I T E Cheatam, D M Ferguson, U C Singh, P Weiner, P Kollman amber 4.1., 1995)."
    },
    {
      "key": "e_1_3_3_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0301-4622(94)00057-3"
    },
    {
      "key": "e_1_3_3_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1088/0953-8984/6/23A/018"
    },
    {
      "key": "e_1_3_3_43_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1063/1.448118"
    },
    {
      "key": "e_1_3_3_44_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/nsb0694-399"
    },
    {
      "key": "e_1_3_3_45_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja962310g"
    },
    {
      "key": "e_1_3_3_46_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1110/ps.8.6.1292"
    },
    {
      "key": "e_1_3_3_47_2",
      "volume-title": "Computer Simulations of Biological Systems",
      "author": "Kollman P A",
      "year": "1997",
      "unstructured": "P A Kollman, R W Dixon, W D Cornell, T Fox, C Chipot, A Pohorille Computer Simulations of Biological Systems, ed W van Gunsteren (ESCOM, Dordrecht, The Netherlands, 1997)."
    }
  ],
  "container-title": "Proceedings of the National Academy of Sciences",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pnas.org/doi/pdf/10.1073/pnas.042496899",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        4,
        12
      ]
    ],
    "date-time": "2022-04-12T13:59:43Z",
    "timestamp": 1649771983000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pnas.org/doi/full/10.1073/pnas.042496899"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2002,
        2,
        26
      ]
    ]
  },
  "references-count": 47,
  "journal-issue": {
    "issue": "5",
    "published-print": {
      "date-parts": [
        [
          2002,
          3,
          5
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1073/pnas.042496899"
  ],
  "URL": "http://dx.doi.org/10.1073/pnas.042496899",
  "relation": {},
  "ISSN": [
    "0027-8424",
    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
  "published": {
    "date-parts": [
      [
        2002,
        2,
        26
      ]
    ]
  },
  "assertion": [
    {
      "value": "2001-09-20",
      "order": 0,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    },
    {
      "value": "2002-02-26",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}