{"data":{"id":"10.6084/m9.figshare.2303449.v1","type":"dois","attributes":{"doi":"10.6084/m9.figshare.2303449.v1","prefix":"10.6084","suffix":"m9.figshare.2303449.v1","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Nash, Anthony","nameType":"Personal","givenName":"Anthony","familyName":"Nash","affiliation":[],"nameIdentifiers":[]},{"name":"Birch, Helen L.","nameType":"Personal","givenName":"Helen L.","familyName":"Birch","affiliation":[],"nameIdentifiers":[]},{"name":"Leeuw, Nora H. De","nameType":"Personal","givenName":"Nora H. De","familyName":"Leeuw","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Mapping intermolecular interactions and active site conformations: from human MMP-1 crystal structure to molecular dynamics free energy calculations"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2016,"subjects":[{"subject":"Biophysics"},{"subject":"Biochemistry"},{"subject":"29999 Physical Sciences not elsewhere classified","subjectScheme":"FOR"},{"subject":"FOS: Physical sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Physical sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Medicine"},{"subject":"Physiology"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Biological sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"39999 Chemical Sciences not elsewhere classified","subjectScheme":"FOR"},{"subject":"FOS: Chemical sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Chemical sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"69999 Biological Sciences not elsewhere classified","subjectScheme":"FOR"},{"subject":"Computational Biology"}],"contributors":[],"dates":[{"date":"2016-02-17","dateType":"Created"},{"date":"2017-02-21","dateType":"Updated"},{"date":"2016","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1080/07391102.2016.1153521","relatedIdentifierType":"DOI"},{"relationType":"IsIdenticalTo","relatedIdentifier":"10.6084/m9.figshare.2303449","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["15609397 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"The zinc-dependent Matrix Metalloproteinases (MMPs) found within the extracellular matrix (ECM) of vertebrates are linked to pathological processes such as arthritis, skin ulceration and cancer. Although a general backbone proteolytic mechanism is understood, crystallographic data continue to suggest an active site that is too narrow to encompass the respective substrate. We present a fully parameterised Molecular Dynamics (MD) study of the structural properties of an MMP-1-collagen crystallographic structure (Protein Data Bank – 4AUO), followed by an exploration of the free energy surface of a collagen polypeptide chain entering the active site, using a combined meta-dynamics and umbrella sampling (MDUS) approach. We conclude that the interactions between MMP-1 and the collagen substrate are in good agreement with a number of experimental studies. As such, our unrestrained MD simulations and our MDUS results, which indicate an energetic barrier for a local uncoiling and insertion event, can inform future investigations of the collagen-peptide non-bonded association steps with the active site prior to proteolytic mechanisms. The elucidation of such free energy barriers provides a better understanding of the role of the enzyme in the ECM and is important in the design of future MMP inhibitors.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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