{"id":1749,"date":"2023-12-14T08:49:43","date_gmt":"2023-12-14T08:49:43","guid":{"rendered":"https:\/\/chemeng.iisc.ac.in\/symposium\/?page_id=1749"},"modified":"2023-12-14T08:49:43","modified_gmt":"2023-12-14T08:49:43","slug":"shivam-tiwari-2","status":"publish","type":"page","link":"https:\/\/chemeng.iisc.ac.in\/symposium\/shivam-tiwari-2\/","title":{"rendered":"SHIVAM TIWARI"},"content":{"rendered":"<p><strong><span style=\"font-size: 18pt;\">Role of Binding Site Specificity in the Disaggregation of Abeta-42 Fibrils via Synthetic Paratope<\/span><\/strong><\/p>\n<p style=\"text-align: left;\">Amyloid-\u03b2 (A\u03b2) fibrils are the characteristic hallmark of Alzheimer\u2019s disease(AD), and most drug development approaches for AD are focused on preventing and reversing the formation of these fibrillar aggregates. Previous studies show that synthetic antibodies have demonstrated great potential to inhibit the A\u03b2 aggregation and disaggregate the preformed A\u03b2 fibrils. Here, we perform explicit molecular dynamics(MD) simulation to elucidate the molecular mechanism of disaggregation of preformed LS-shaped A\u03b2 42 protofibril with a flex-<br \/>\nible, hairpin-like synthetic paratope (SP) which, in a recent experimental study, has shown promising results. Our simulations demonstrate various potential binding sites for SP on A\u03b2 42 protofibril. However, binding of SP at the amyloidogenic core region (KLVFF) shows pronounced structural disruption of A\u03b2 42 protofibril. Our results show heavy loss of \u03b2 sheet content, dismantling of K28-A42 salt bridge, and destruction of key contacts in the hydrophobic cores of A\u03b2 42 protofibril in the presence of SP. We found the aromatic and hydrophobic residues of A\u03b2 42 protofibril participating primarily in the binding with SP. Also, we found that \u03c0 \u2212 \u03c0 stacking and hydrophobic interactions are the most dominant mode of interaction between SP and A\u03b2 42 protofibril. This work provides a detailed atomistic perspective on the A\u03b2 42 protofibril disaggregation mechanism with SP, and the findings can help develop more effective drugs for AD in the future.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Role of Binding Site Specificity in the Disaggregation of Abeta-42 Fibrils via Synthetic Paratope Amyloid-\u03b2 (A\u03b2) fibrils are the characteristic hallmark of Alzheimer\u2019s disease(AD), and most drug development approaches for AD are focused on preventing and reversing the formation of these fibrillar aggregates. Previous studies show that synthetic antibodies have demonstrated great potential to inhibit the A\u03b2 aggregation and disaggregate [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"_links":{"self":[{"href":"https:\/\/chemeng.iisc.ac.in\/symposium\/wp-json\/wp\/v2\/pages\/1749"}],"collection":[{"href":"https:\/\/chemeng.iisc.ac.in\/symposium\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/chemeng.iisc.ac.in\/symposium\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/chemeng.iisc.ac.in\/symposium\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/chemeng.iisc.ac.in\/symposium\/wp-json\/wp\/v2\/comments?post=1749"}],"version-history":[{"count":1,"href":"https:\/\/chemeng.iisc.ac.in\/symposium\/wp-json\/wp\/v2\/pages\/1749\/revisions"}],"predecessor-version":[{"id":1751,"href":"https:\/\/chemeng.iisc.ac.in\/symposium\/wp-json\/wp\/v2\/pages\/1749\/revisions\/1751"}],"wp:attachment":[{"href":"https:\/\/chemeng.iisc.ac.in\/symposium\/wp-json\/wp\/v2\/media?parent=1749"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}