{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T03:46:33Z","timestamp":1778816793766,"version":"3.51.4"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2013,1,1]],"date-time":"2013-01-01T00:00:00Z","timestamp":1356998400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2013]]},"abstract":"<jats:p>A major genetic suspect for Alzheimer\u2019s disease is the pathological conformation assumed by apolipoprotein E4 (ApoE4) through intramolecular interaction. In the present study, a large library of natural compounds was screened against ApoE4 to identify novel therapeutic molecules that can prevent ApoE4 from being converted to its pathological conformation. We report two such natural compounds PHC and IAH that bound to the active site of ApoE4 during the docking process. The binding analysis suggested that they have a strong mechanistic ability to correct the pathological structural orientation of ApoE4 by preventing repulsion between Arg 61 and Arg 112, thus inhibiting the formation of a salt bridge between Arg 61 and Glu 255. However, when the molecular dynamics simulations were carried out, structural changes in the PHC-bound complex forced PHC to move out of the cavity thus destabilizing the complex. However, IAH was structurally stable inside the binding pocket throughout the simulations trajectory. Our simulations results indicate that the initial receptor-ligand interaction observed after docking could be limited due to the receptor rigid docking algorithm and that the conformations and interactions observed after simulation runs are more energetically favored and should be better representations of derivative poses in the receptor.<\/jats:p>","DOI":"10.1155\/2013\/620793","type":"journal-article","created":{"date-parts":[[2013,11,13]],"date-time":"2013-11-13T21:21:57Z","timestamp":1384377717000},"page":"1-8","source":"Crossref","is-referenced-by-count":15,"title":["Novel Natural Structure Corrector of ApoE4 for Checking Alzheimer\u2019s Disease: Benefits from High Throughput Screening and Molecular Dynamics Simulations"],"prefix":"10.1155","volume":"2013","author":[{"given":"Manisha","family":"Goyal","sequence":"first","affiliation":[{"name":"Apaji Institute of Mathematics & Applied Computer Technology, Banasthali University, Tonk, Rajasthan 304022, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonam","family":"Grover","sequence":"additional","affiliation":[{"name":"School of Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4226-3063","authenticated-orcid":true,"given":"Jaspreet Kaur","family":"Dhanjal","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Delhi Technological University, New Delhi 110042, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sukriti","family":"Goyal","sequence":"additional","affiliation":[{"name":"Apaji Institute of Mathematics & Applied Computer Technology, Banasthali University, Tonk, Rajasthan 304022, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7067-4770","authenticated-orcid":true,"given":"Chetna","family":"Tyagi","sequence":"additional","affiliation":[{"name":"Apaji Institute of Mathematics & Applied Computer Technology, Banasthali University, Tonk, Rajasthan 304022, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1857-7003","authenticated-orcid":true,"given":"Sajeev","family":"Chacko","sequence":"additional","affiliation":[{"name":"Thematic Unit of Excellence on Computational Materials Science, S. 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