DOI: 10.1063/1.2393236. The free energy landscape of small peptides as obtained from metadynamics with umbrella sampling corrections

The free energy landscape of small peptides as obtained from metadynamics with umbrella sampling corrections

10.1063/1.2393236

Crossref journal-article

AIP Publishing

The Journal of Chemical Physics (317)

Abstract

There is considerable interest in developing methodologies for the accurate evaluation of free energies, especially in the context of biomolecular simulations. Here, we report on a reexamination of the recently developed metadynamics method, which is explicitly designed to probe “rare events” and areas of phase space that are typically difficult to access with a molecular dynamics simulation. Specifically, we show that the accuracy of the free energy landscape calculated with the metadynamics method may be considerably improved when combined with umbrella sampling techniques. As test cases, we have studied the folding free energy landscape of two prototypical peptides: Ace-(Gly)2-Pro-(Gly)3-Nme in vacuo and trialanine solvated by both implicit and explicit water. The method has been implemented in the classical biomolecular code AMBER and is to be distributed in the next scheduled release of the code.

Bibliography

Babin, V., Roland, C., Darden, T. A., & Sagui, C. (2006). The free energy landscape of small peptides as obtained from metadynamics with umbrella sampling corrections. The Journal of Chemical Physics, 125(20).

Authors 4

Volodymyr Babin (first)
Christopher Roland (additional)
Thomas A. Darden (additional)
Celeste Sagui (additional)

References 45 Referenced 80

{'volume-title': 'Lecture Notes in Computational Science and Engineering', 'year': '2004', 'author': 'Attinger', 'key': '2023080102215719800_c1'} / Lecture Notes in Computational Science and Engineering by Attinger (2004)
10.1063/1.1410978 / J. Chem. Phys. (2001)
10.1063/1.1308516 / J. Phys. Chem. (2000)
10.1016/S0009-2614(97)01198-6 / Chem. Phys. Lett. (1997)
10.1016/S0009-2614(99)01123-9 / Chem. Phys. Lett. (1999)
10.1002/jcc.540130812 / J. Comput. Chem. (1992)
10.1063/1.480139 / J. Chem. Phys. (1999)
10.1016/0021-9991(87)90054-4 / J. Comput. Phys. (1987)
10.1063/1.463947 / J. Chem. Phys. (1992)
10.1002/(SICI)1096-987X(199709)18:12<1450::AID-JCC3>3.0.CO;2-I / J. Comput. Chem. (1997)
10.1073/pnas.202427399 / Proc. Natl. Acad. Sci. U.S.A. (2002)
10.1103/PhysRevLett.90.238302 / Phys. Rev. Lett. (2003)
10.1103/PhysRevLett.55.2471 / Phys. Rev. Lett. (1985)
10.1063/1.439486 / J. Chem. Phys. (1980)
10.1080/00268978400101201 / Mol. Phys. (1984)
10.1007/BF00124016 / J. Comput.-Aided Mol. Des. (1994)
10.1063/1.1574777 / J. Chem. Phys. (2003)
10.1103/PhysRevLett.86.2050 / Phys. Rev. Lett. (2001)
10.1021/ja048285t / J. Am. Chem. Soc. (2004)
10.1021/jp037935x / J. Phys. Chem. B (2004)
10.1021/ja0445950 / J. Am. Chem. Soc. (2005)
10.1529/biophysj.103.037283 / Biophys. J. (2004)
10.1103/PhysRevLett.93.025901 / Phys. Rev. Lett. (2004)
10.1002/cphc.200400063 / ChemPhysChem (2004)
10.1021/jp053428z / J. Phys. Chem. A (2005)
10.1021/jp055809i / J. Phys. Chem. B (2006)
10.1063/1.1940029 / J. Chem. Phys. (2005)
{'year': '2004', 'key': '2023080102215719800_c28'} (2004)
10.1016/S0959-440X(03)00040-X / Curr. Opin. Struct. Biol. (2003)
10.1002/1097-0134(20010215)42:3<345::AID-PROT50>3.0.CO;2-H / Proteins (2001)
10.1073/pnas.201543998 / Proc. Natl. Acad. Sci. U.S.A. (2001)
10.1063/1.2138694 / J. Chem. Phys. (2005)
{'key': '2023080102215719800_c33'}
10.1145/361002.361007 / Commun. ACM (1975)
10.1021/jp045571i / J. Phys. Chem. B (2005)
10.1103/PhysRevLett.96.090601 / Phys. Rev. Lett. (2006)
10.1021/jp972280j / J. Phys. Chem. B (1998)
10.1021/ja00124a002 / J. Am. Chem. Soc. (1995)
10.1063/1.448118 / J. Chem. Phys. (1984)
10.1063/1.464397 / J. Chem. Phys. (1993)
10.1063/1.470117 / J. Chem. Phys. (1995)
10.1063/1.445869 / J. Chem. Phys. (1983)
10.1002/jcc.10313 / J. Comput. Chem. (2003)
10.1145/62038.69651 / ACM Trans. Math. Softw. (1989)
{'key': '2023080102215719800_c45'}

Dates

Type	When
Created	18 years, 8 months ago (Nov. 30, 2006, 10:55 a.m.)
Deposited	2 years ago (July 31, 2023, 10:22 p.m.)
Indexed	4 weeks, 1 day ago (July 30, 2025, 6:47 a.m.)
Issued	18 years, 9 months ago (Nov. 28, 2006)
Published	18 years, 9 months ago (Nov. 28, 2006)
Published Online	18 years, 9 months ago (Nov. 28, 2006)
Published Print	18 years, 9 months ago (Nov. 28, 2006)

Funders 0

None

BibTeX

@article{Babin_2006, title={The free energy landscape of small peptides as obtained from metadynamics with umbrella sampling corrections}, volume={125}, ISSN={1089-7690}, url={http://dx.doi.org/10.1063/1.2393236}, DOI={10.1063/1.2393236}, number={20}, journal={The Journal of Chemical Physics}, publisher={AIP Publishing}, author={Babin, Volodymyr and Roland, Christopher and Darden, Thomas A. and Sagui, Celeste}, year={2006}, month=nov }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        30
      ]
    ],
    "date-time": "2025-07-30T10:47:52Z",
    "timestamp": 1753872472297,
    "version": "3.41.2"
  },
  "reference-count": 45,
  "publisher": "AIP Publishing",
  "issue": "20",
  "content-domain": {
    "domain": [
      "pubs.aip.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2006,
        11,
        28
      ]
    ]
  },
  "abstract": "<jats:p>There is considerable interest in developing methodologies for the accurate evaluation of free energies, especially in the context of biomolecular simulations. Here, we report on a reexamination of the recently developed metadynamics method, which is explicitly designed to probe \u201crare events\u201d and areas of phase space that are typically difficult to access with a molecular dynamics simulation. Specifically, we show that the accuracy of the free energy landscape calculated with the metadynamics method may be considerably improved when combined with umbrella sampling techniques. As test cases, we have studied the folding free energy landscape of two prototypical peptides: Ace-(Gly)2-Pro-(Gly)3-Nme\u2008in vacuo and trialanine solvated by both implicit and explicit water. The method has been implemented in the classical biomolecular code AMBER and is to be distributed in the next scheduled release of the code.</jats:p>",
  "DOI": "10.1063/1.2393236",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2006,
        11,
        30
      ]
    ],
    "date-time": "2006-11-30T15:55:13Z",
    "timestamp": 1164902113000
  },
  "update-policy": "https://doi.org/10.1063/aip-crossmark-policy-page",
  "source": "Crossref",
  "is-referenced-by-count": 80,
  "title": "The free energy landscape of small peptides as obtained from metadynamics with umbrella sampling corrections",
  "prefix": "10.1063",
  "volume": "125",
  "author": [
    {
      "given": "Volodymyr",
      "family": "Babin",
      "sequence": "first",
      "affiliation": [
        {
          "name": "North Carolina State University Center for High Performance Simulations (CHiPS), , Raleigh, North Carolina 27695 and Department of Physics, , Raleigh, North Carolina 27695"
        },
        {
          "name": "North Carolina State University Center for High Performance Simulations (CHiPS), , Raleigh, North Carolina 27695 and Department of Physics, , Raleigh, North Carolina 27695"
        }
      ]
    },
    {
      "given": "Christopher",
      "family": "Roland",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "North Carolina State University Center for High Performance Simulations (CHiPS), , Raleigh, North Carolina 27695 and Department of Physics, , Raleigh, North Carolina 27695"
        },
        {
          "name": "North Carolina State University Center for High Performance Simulations (CHiPS), , Raleigh, North Carolina 27695 and Department of Physics, , Raleigh, North Carolina 27695"
        }
      ]
    },
    {
      "given": "Thomas A.",
      "family": "Darden",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "National Institute of Environmental Health Sciences , Research Triangle Park, North Carolina 27709"
        }
      ]
    },
    {
      "given": "Celeste",
      "family": "Sagui",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "North Carolina State University Center for High Performance Simulations (CHiPS), , Raleigh, North Carolina 27695 and Department of Physics, , Raleigh, North Carolina 27695"
        },
        {
          "name": "North Carolina State University Center for High Performance Simulations (CHiPS), , Raleigh, North Carolina 27695 and Department of Physics, , Raleigh, North Carolina 27695"
        }
      ]
    }
  ],
  "member": "317",
  "published-online": {
    "date-parts": [
      [
        2006,
        11,
        28
      ]
    ]
  },
  "reference": [
    {
      "volume-title": "Lecture Notes in Computational Science and Engineering",
      "year": "2004",
      "author": "Attinger",
      "key": "2023080102215719800_c1"
    },
    {
      "key": "2023080102215719800_c2",
      "doi-asserted-by": "publisher",
      "first-page": "9169",
      "DOI": "10.1063/1.1410978",
      "volume": "115",
      "year": "2001",
      "journal-title": "J. Chem. Phys."
    },
    {
      "key": "2023080102215719800_c3",
      "doi-asserted-by": "publisher",
      "first-page": "6042",
      "DOI": "10.1063/1.1308516",
      "volume": "113",
      "year": "2000",
      "journal-title": "J. Phys. Chem."
    },
    {
      "key": "2023080102215719800_c4",
      "doi-asserted-by": "publisher",
      "first-page": "140",
      "DOI": "10.1016/S0009-2614(97)01198-6",
      "volume": "281",
      "year": "1997",
      "journal-title": "Chem. Phys. Lett."
    },
    {
      "key": "2023080102215719800_c5",
      "doi-asserted-by": "publisher",
      "first-page": "141",
      "DOI": "10.1016/S0009-2614(99)01123-9",
      "volume": "314",
      "year": "1999",
      "journal-title": "Chem. Phys. Lett."
    },
    {
      "key": "2023080102215719800_c6",
      "doi-asserted-by": "publisher",
      "first-page": "1011",
      "DOI": "10.1002/jcc.540130812",
      "volume": "13",
      "year": "1992",
      "journal-title": "J. Comput. Chem."
    },
    {
      "key": "2023080102215719800_c7",
      "doi-asserted-by": "publisher",
      "first-page": "8048",
      "DOI": "10.1063/1.480139",
      "volume": "111",
      "year": "1999",
      "journal-title": "J. Chem. Phys."
    },
    {
      "key": "2023080102215719800_c8",
      "doi-asserted-by": "publisher",
      "first-page": "237",
      "DOI": "10.1016/0021-9991(87)90054-4",
      "volume": "68",
      "year": "1987",
      "journal-title": "J. Comput. Phys."
    },
    {
      "key": "2023080102215719800_c9",
      "doi-asserted-by": "publisher",
      "first-page": "6690",
      "DOI": "10.1063/1.463947",
      "volume": "97",
      "year": "1992",
      "journal-title": "J. Chem. Phys."
    },
    {
      "key": "2023080102215719800_c10",
      "doi-asserted-by": "publisher",
      "first-page": "1450",
      "DOI": "10.1002/(SICI)1096-987X(199709)18:12&lt;1450::AID-JCC3&gt;3.0.CO;2-I",
      "volume": "18",
      "year": "1997",
      "journal-title": "J. Comput. Chem."
    },
    {
      "key": "2023080102215719800_c11",
      "doi-asserted-by": "publisher",
      "first-page": "12562",
      "DOI": "10.1073/pnas.202427399",
      "volume": "99",
      "year": "2002",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "2023080102215719800_c12",
      "doi-asserted-by": "publisher",
      "first-page": "238302",
      "DOI": "10.1103/PhysRevLett.90.238302",
      "volume": "90",
      "year": "2003",
      "journal-title": "Phys. Rev. Lett."
    },
    {
      "key": "2023080102215719800_c13",
      "doi-asserted-by": "publisher",
      "first-page": "2471",
      "DOI": "10.1103/PhysRevLett.55.2471",
      "volume": "55",
      "year": "1985",
      "journal-title": "Phys. Rev. Lett."
    },
    {
      "key": "2023080102215719800_c14",
      "doi-asserted-by": "publisher",
      "first-page": "2384",
      "DOI": "10.1063/1.439486",
      "volume": "72",
      "year": "1980",
      "journal-title": "J. Chem. Phys."
    },
    {
      "key": "2023080102215719800_c15",
      "doi-asserted-by": "publisher",
      "first-page": "255",
      "DOI": "10.1080/00268978400101201",
      "volume": "52",
      "year": "1984",
      "journal-title": "Mol. Phys."
    },
    {
      "key": "2023080102215719800_c16",
      "doi-asserted-by": "publisher",
      "first-page": "695",
      "DOI": "10.1007/BF00124016",
      "volume": "8",
      "year": "1994",
      "journal-title": "J. Comput.-Aided Mol. Des."
    },
    {
      "key": "2023080102215719800_c17",
      "doi-asserted-by": "publisher",
      "first-page": "10762",
      "DOI": "10.1063/1.1574777",
      "volume": "118",
      "year": "2003",
      "journal-title": "J. Chem. Phys."
    },
    {
      "key": "2023080102215719800_c18",
      "doi-asserted-by": "publisher",
      "first-page": "2050",
      "DOI": "10.1103/PhysRevLett.86.2050",
      "volume": "86",
      "year": "2001",
      "journal-title": "Phys. Rev. Lett."
    },
    {
      "key": "2023080102215719800_c19",
      "doi-asserted-by": "publisher",
      "first-page": "9492",
      "DOI": "10.1021/ja048285t",
      "volume": "126",
      "year": "2004",
      "journal-title": "J. Am. Chem. Soc."
    },
    {
      "key": "2023080102215719800_c20",
      "doi-asserted-by": "publisher",
      "first-page": "11567",
      "DOI": "10.1021/jp037935x",
      "volume": "108",
      "year": "2004",
      "journal-title": "J. Phys. Chem. B"
    },
    {
      "key": "2023080102215719800_c21",
      "doi-asserted-by": "publisher",
      "first-page": "2600",
      "DOI": "10.1021/ja0445950",
      "volume": "124",
      "year": "2005",
      "journal-title": "J. Am. Chem. Soc."
    },
    {
      "key": "2023080102215719800_c22",
      "doi-asserted-by": "publisher",
      "first-page": "58",
      "DOI": "10.1529/biophysj.103.037283",
      "volume": "87",
      "year": "2004",
      "journal-title": "Biophys. J."
    },
    {
      "key": "2023080102215719800_c23",
      "doi-asserted-by": "publisher",
      "first-page": "025901",
      "DOI": "10.1103/PhysRevLett.93.025901",
      "volume": "93",
      "year": "2004",
      "journal-title": "Phys. Rev. Lett."
    },
    {
      "key": "2023080102215719800_c24",
      "doi-asserted-by": "publisher",
      "first-page": "1558",
      "DOI": "10.1002/cphc.200400063",
      "volume": "5",
      "year": "2004",
      "journal-title": "ChemPhysChem"
    },
    {
      "key": "2023080102215719800_c25",
      "doi-asserted-by": "publisher",
      "first-page": "7682",
      "DOI": "10.1021/jp053428z",
      "volume": "109",
      "year": "2005",
      "journal-title": "J. Phys. Chem. A"
    },
    {
      "key": "2023080102215719800_c26",
      "doi-asserted-by": "publisher",
      "first-page": "2325",
      "DOI": "10.1021/jp055809i",
      "volume": "110",
      "year": "2006",
      "journal-title": "J. Phys. Chem. B"
    },
    {
      "key": "2023080102215719800_c27",
      "doi-asserted-by": "publisher",
      "first-page": "244507",
      "DOI": "10.1063/1.1940029",
      "volume": "122",
      "year": "2005",
      "journal-title": "J. Chem. Phys."
    },
    {
      "year": "2004",
      "key": "2023080102215719800_c28"
    },
    {
      "key": "2023080102215719800_c29",
      "doi-asserted-by": "publisher",
      "first-page": "168",
      "DOI": "10.1016/S0959-440X(03)00040-X",
      "volume": "13",
      "year": "2003",
      "journal-title": "Curr. Opin. Struct. Biol."
    },
    {
      "key": "2023080102215719800_c30",
      "doi-asserted-by": "publisher",
      "first-page": "345",
      "DOI": "10.1002/1097-0134(20010215)42:3&lt;345::AID-PROT50&gt;3.0.CO;2-H",
      "volume": "42",
      "year": "2001",
      "journal-title": "Proteins"
    },
    {
      "key": "2023080102215719800_c31",
      "doi-asserted-by": "publisher",
      "first-page": "14931",
      "DOI": "10.1073/pnas.201543998",
      "volume": "96",
      "year": "2001",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "2023080102215719800_c32",
      "doi-asserted-by": "publisher",
      "first-page": "244906",
      "DOI": "10.1063/1.2138694",
      "volume": "123",
      "year": "2005",
      "journal-title": "J. Chem. Phys."
    },
    {
      "key": "2023080102215719800_c33"
    },
    {
      "key": "2023080102215719800_c34",
      "doi-asserted-by": "publisher",
      "first-page": "509",
      "DOI": "10.1145/361002.361007",
      "volume": "18",
      "year": "1975",
      "journal-title": "Commun. ACM"
    },
    {
      "key": "2023080102215719800_c35",
      "doi-asserted-by": "publisher",
      "first-page": "6676",
      "DOI": "10.1021/jp045571i",
      "volume": "109",
      "year": "2005",
      "journal-title": "J. Phys. Chem. B"
    },
    {
      "key": "2023080102215719800_c36",
      "doi-asserted-by": "publisher",
      "first-page": "090601",
      "DOI": "10.1103/PhysRevLett.96.090601",
      "volume": "96",
      "year": "2006",
      "journal-title": "Phys. Rev. Lett."
    },
    {
      "key": "2023080102215719800_c37",
      "doi-asserted-by": "publisher",
      "first-page": "865",
      "DOI": "10.1021/jp972280j",
      "volume": "102",
      "year": "1998",
      "journal-title": "J. Phys. Chem. B"
    },
    {
      "key": "2023080102215719800_c38",
      "doi-asserted-by": "publisher",
      "first-page": "5179",
      "DOI": "10.1021/ja00124a002",
      "volume": "117",
      "year": "1995",
      "journal-title": "J. Am. Chem. Soc."
    },
    {
      "key": "2023080102215719800_c39",
      "doi-asserted-by": "publisher",
      "first-page": "3684",
      "DOI": "10.1063/1.448118",
      "volume": "81",
      "year": "1984",
      "journal-title": "J. Chem. Phys."
    },
    {
      "key": "2023080102215719800_c40",
      "doi-asserted-by": "publisher",
      "first-page": "10089",
      "DOI": "10.1063/1.464397",
      "volume": "98",
      "year": "1993",
      "journal-title": "J. Chem. Phys."
    },
    {
      "key": "2023080102215719800_c41",
      "doi-asserted-by": "publisher",
      "first-page": "8577",
      "DOI": "10.1063/1.470117",
      "volume": "103",
      "year": "1995",
      "journal-title": "J. Chem. Phys."
    },
    {
      "key": "2023080102215719800_c42",
      "doi-asserted-by": "publisher",
      "first-page": "926",
      "DOI": "10.1063/1.445869",
      "volume": "79",
      "year": "1983",
      "journal-title": "J. Chem. Phys."
    },
    {
      "key": "2023080102215719800_c43",
      "doi-asserted-by": "publisher",
      "first-page": "1437",
      "DOI": "10.1002/jcc.10313",
      "volume": "24",
      "year": "2003",
      "journal-title": "J. Comput. Chem."
    },
    {
      "key": "2023080102215719800_c44",
      "doi-asserted-by": "publisher",
      "first-page": "79",
      "DOI": "10.1145/62038.69651",
      "volume": "15",
      "year": "1989",
      "journal-title": "ACM Trans. Math. Softw."
    },
    {
      "key": "2023080102215719800_c45"
    }
  ],
  "container-title": "The Journal of Chemical Physics",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://pubs.aip.org/aip/jcp/article-pdf/doi/10.1063/1.2393236/15391814/204909_1_online.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://pubs.aip.org/aip/jcp/article-pdf/doi/10.1063/1.2393236/15391814/204909_1_online.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        8,
        1
      ]
    ],
    "date-time": "2023-08-01T02:22:09Z",
    "timestamp": 1690856529000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://pubs.aip.org/jcp/article/125/20/204909/916754/The-free-energy-landscape-of-small-peptides-as"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2006,
        11,
        28
      ]
    ]
  },
  "references-count": 45,
  "journal-issue": {
    "issue": "20",
    "published-print": {
      "date-parts": [
        [
          2006,
          11,
          28
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1063/1.2393236",
  "relation": {},
  "ISSN": [
    "0021-9606",
    "1089-7690"
  ],
  "subject": [],
  "published-other": {
    "date-parts": [
      [
        2006,
        11,
        28
      ]
    ]
  },
  "published": {
    "date-parts": [
      [
        2006,
        11,
        28
      ]
    ]
  },
  "article-number": "204909"
}