{"id":1752,"date":"2025-07-16T13:42:30","date_gmt":"2025-07-16T13:42:30","guid":{"rendered":"https:\/\/www.tifrh.res.in\/~sciencemedia\/?p=1752"},"modified":"2025-07-16T13:42:35","modified_gmt":"2025-07-16T13:42:35","slug":"phdone-studying-protein-conformational-dynamics-over-large-timescales","status":"publish","type":"post","link":"https:\/\/www.tifrh.res.in\/~sciencemedia\/index.php\/2025\/07\/16\/phdone-studying-protein-conformational-dynamics-over-large-timescales\/","title":{"rendered":"#PhDone: Studying protein conformational dynamics over large timescales"},"content":{"rendered":"\n

Congratulations to Nihar Khandave on successfully defending his thesis titled \u2018Extending CEST NMR experiments to study protein conformational dynamics occurring over the ~10-4<\/sup>\u00a0to ~100<\/sup>\u00a0seconds timescale\u2019.<\/p>\n\n\n\n

\"\"<\/figure>
\n

Proteins can exist in\u00a0multiple three-dimensional conformations. Often, the most stable native conformation is prevalent while less populated ‘excited’ states exist in equilibrium with native state and each other. The protein molecule has to\u00a0switch\u00a0between these different conformations to perform various tasks (such as binding to ligands like a drug molecule or interaction with other proteins etc.). Understanding the underlying dynamics between the\u00a0native conformation\u00a0and\u00a0excited conformation(s)\u00a0can help provide crucial insights into protein activity and folding.<\/p>\n<\/div><\/div>\n\n\n\n

As far as conformational dynamics is concerned, these\u00a0excited transient states\u00a0are often\u00a0short-lived\u00a0with lifetimes from microseconds (~1000000 exchange events in a second; fast dynamics) to seconds (~1 exchange event in a second; slow dynamics).<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

<\/p>\n\n\n\n

How transient are these excited states?<\/em>
<\/strong>– <\/em>Short lifetimes of \u2018excited\u2019 states:<\/em> \u2018~1000000 exchange events in a second\u2019 = The excited state changes into the native state and back (in a continuous cycle) for approximate 1000000 times in a second.<\/em>
– Long(er) lifetimes<\/em>: \u2018~1 exchange event in a second\u2019 = The excited state changes into the native state and back once in a second.<\/em><\/p>\n\n\n\n

Due to the transient nature of the excited states, they are\u00a0not directly observable\u00a0through conventional NMR experiments (or conventional biophysical techniques) and therefore need specialized NMR experiments. Typically, different NMR experiments are used for studying slow, intermediate and fast conformational dynamics, but here Nihar shows that the\u00a0Chemical Exchange Saturation Transfer (CEST) NMR\u00a0<\/strong>experiments can be used to study protein conformational dynamics spanning a\u00a0broad range of timescale (1 to 10,000 exchange events per second). He demonstrates this process to observe transient populations of \u2018excited\u2019 conformations in three proteins: FF domain, T4 Lysozyme and the peripheral subunit binding domain (PSBD).<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Read more about Nihar\u2019s work at:<\/p>\n\n\n\n

– Using the amide\u00a015<\/sup>N CEST NMR experiment to study slow exchange between \u2018visible\u2019 protein states<\/a>
– Studying micro to millisecond protein dynamics using simple amide\u00a015<\/sup>N CEST experiments supplemented with major-state\u00a0R<\/em>2<\/em><\/sub>\u00a0and visible peak-position constraints<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Congratulations to Nihar Khandave on successfully defending his thesis titled \u2018Extending CEST NMR experiments to study protein conformational dynamics occurring over the ~10-4\u00a0to ~100\u00a0seconds timescale\u2019.…<\/p>\n","protected":false},"author":2,"featured_media":1759,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[2],"tags":[],"_links":{"self":[{"href":"https:\/\/www.tifrh.res.in\/~sciencemedia\/index.php\/wp-json\/wp\/v2\/posts\/1752"}],"collection":[{"href":"https:\/\/www.tifrh.res.in\/~sciencemedia\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.tifrh.res.in\/~sciencemedia\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.tifrh.res.in\/~sciencemedia\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.tifrh.res.in\/~sciencemedia\/index.php\/wp-json\/wp\/v2\/comments?post=1752"}],"version-history":[{"count":1,"href":"https:\/\/www.tifrh.res.in\/~sciencemedia\/index.php\/wp-json\/wp\/v2\/posts\/1752\/revisions"}],"predecessor-version":[{"id":1760,"href":"https:\/\/www.tifrh.res.in\/~sciencemedia\/index.php\/wp-json\/wp\/v2\/posts\/1752\/revisions\/1760"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.tifrh.res.in\/~sciencemedia\/index.php\/wp-json\/wp\/v2\/media\/1759"}],"wp:attachment":[{"href":"https:\/\/www.tifrh.res.in\/~sciencemedia\/index.php\/wp-json\/wp\/v2\/media?parent=1752"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.tifrh.res.in\/~sciencemedia\/index.php\/wp-json\/wp\/v2\/categories?post=1752"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.tifrh.res.in\/~sciencemedia\/index.php\/wp-json\/wp\/v2\/tags?post=1752"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}