{"data":{"id":"10.6084/m9.figshare.c.2091347","type":"dois","attributes":{"doi":"10.6084/m9.figshare.c.2091347","prefix":"10.6084","suffix":"m9.figshare.c.2091347","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Hezekiel M. Kumalo","affiliation":[],"nameIdentifiers":[]},{"name":"Soumendranath Bhakat","affiliation":[],"nameIdentifiers":[]},{"name":"Soliman, Mahmoud E.","nameType":"Personal","givenName":"Mahmoud E.","familyName":"Soliman","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Investigation of flap flexibility of β-secretase using molecular dynamic simulations"}],"publisher":"Figshare","container":{},"publicationYear":2015,"subjects":[{"subject":"Biophysics"},{"subject":"Biochemistry"},{"subject":"Molecular Biology"},{"subject":"Pharmacology"},{"subject":"Biotechnology"},{"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":"Sociology"},{"subject":"FOS: Sociology","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Sociology","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"69999 Biological Sciences not elsewhere classified","subjectScheme":"FOR"},{"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":"Computational Biology"}],"contributors":[],"dates":[{"date":"2015-12-05","dateType":"Created"},{"date":"2016-05-20","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1080/07391102.2015.1064831","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"CC-BY","rightsUri":"http://creativecommons.org/licenses/by/3.0/us"}],"descriptions":[{"description":"Flap motif and its dynamics were extensively reported in aspartate proteases, e.g. HIV proteases and plasmepsins. Herein, we report the first account of flap dynamics amongst different conformations of β-secretase using molecular dynamics simulation. Various parameters were proposed and a selected few were picked which could appropriately describe the flap motion. Three systems were studied, namely Free (BACE\u003csub\u003eFree\u003c/sub\u003e) and two ligand-bound conformations, which belonged to space groups P6\u003csub\u003e1\u003c/sub\u003e22 (BACE\u003csub\u003eBound1\u003c/sub\u003e) and C222\u003csub\u003e1\u003c/sub\u003e (BACE\u003csub\u003eBound2\u003c/sub\u003e), respectively and four parameters (distance between the flaps tip residue, Thr72 and Ser325, \u003ci\u003ed\u003c/i\u003e\u003csub\u003e1\u003c/sub\u003e; dihedral angle, \u003ci\u003eϕ\u003c/i\u003e (Thr72-Asp32-Asp228-Ser325); TriCα angles, \u003ci\u003eθ\u003c/i\u003e\u003csub\u003e1\u003c/sub\u003e (Thr72-Asp32-Ser325), and \u003ci\u003eθ\u003c/i\u003e\u003csub\u003e2\u003c/sub\u003e (Thr72-Asp228-Ser325)) were proposed to understand the change in dynamics of flap domain and the extent of flap opening and closing. Analysis of, \u003ci\u003eθ\u003c/i\u003e\u003csub\u003e2\u003c/sub\u003e, \u003ci\u003ed\u003c/i\u003e\u003csub\u003e1\u003c/sub\u003e, \u003ci\u003eθ\u003c/i\u003e\u003csub\u003e1\u003c/sub\u003e and \u003ci\u003eϕ\u003c/i\u003e confirmed that the BACE\u003csub\u003eFree\u003c/sub\u003e adopted semi-open, open and closed conformations with slight twisting during flap opening. However, BACE\u003csub\u003eBound1\u003c/sub\u003e (P6122) showed an adaptation to open conformation due to lack of hydrogen bond interaction between the ligand and flap tip residue. A slight flap \u003ci\u003etwisting, ϕ\u003c/i\u003e (\u003ci\u003elateral twisting\u003c/i\u003e) was observed for BACE\u003csub\u003eBound1\u003c/sub\u003e during flap opening which correlates with the opening of BACE\u003csub\u003eFree\u003c/sub\u003e. Contradictory to the BACE\u003csub\u003eBound1\u003c/sub\u003e, the BACE\u003csub\u003eBound2\u003c/sub\u003e locked the flap in a closed conformation throughout the simulation due to formation of a stable hydrogen bond interaction between the flap tip residue and ligand. Analyses of all three systems highlight that \u003ci\u003ed\u003c/i\u003e\u003csub\u003e1\u003c/sub\u003e, \u003ci\u003eθ\u003c/i\u003e\u003csub\u003e2\u003c/sub\u003e and \u003ci\u003eϕ\u003c/i\u003e can be precisely used to describe the extent of flap opening and closing concurrently with snapshots along the molecular dynamics trajectory across several conformations of β-secretase.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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","url":"https://figshare.com/collections/Investigation_of_flap_flexibility_of_secretase_using_molecular_dynamic_simulations/2091347","contentUrl":null,"metadataVersion":3,"schemaVersion":"http://datacite.org/schema/kernel-4","source":"api","isActive":true,"state":"findable","reason":null,"viewCount":0,"viewsOverTime":[],"downloadCount":0,"downloadsOverTime":[],"referenceCount":0,"citationCount":0,"citationsOverTime":[],"partCount":0,"partOfCount":0,"versionCount":0,"versionOfCount":0,"created":"2015-12-05T18:06:06.000Z","registered":"2015-12-05T18:06:07.000Z","published":"2015","updated":"2024-12-12T14:22:53.000Z"},"relationships":{"client":{"data":{"id":"figshare.ars","type":"clients"}},"provider":{"data":{"id":"otjm","type":"providers"}},"media":{"data":{"id":"10.6084/m9.figshare.c.2091347","type":"media"}},"references":{"data":[]},"citations":{"data":[]},"parts":{"data":[]},"partOf":{"data":[]},"versions":{"data":[]},"versionOf":{"data":[]}}}}