{"id":812,"date":"2023-10-30T08:20:33","date_gmt":"2023-10-30T08:20:33","guid":{"rendered":"https:\/\/todaysainews.com\/index.php\/2023\/10\/30\/alphafold-unlocks-one-of-the-greatest-puzzles-in-biology\/"},"modified":"2025-04-27T07:32:03","modified_gmt":"2025-04-27T07:32:03","slug":"alphafold-unlocks-one-of-the-greatest-puzzles-in-biology","status":"publish","type":"post","link":"https:\/\/todaysainews.com\/index.php\/2023\/10\/30\/alphafold-unlocks-one-of-the-greatest-puzzles-in-biology\/","title":{"rendered":"AlphaFold unlocks one of the greatest puzzles in biology"},"content":{"rendered":"<p> [ad_1]<br \/>\n<\/p>\n<div>\n<div class=\"article-cover article-cover--centered\">\n<div class=\"article-cover__header\">\n<p class=\"article-cover__eyebrow glue-label\">Impact<\/p>\n<dl class=\"article-cover__meta\">\n<dt class=\"glue-visually-hidden\">Published<\/dt>\n<dd class=\"article-cover__date glue-label\">\n              <time datetime=\"2022-07-28\"><br \/>\n                28 July 2022<br \/>\n              <\/time>\n            <\/dd>\n<\/dl>\n<section class=\"glue-social glue-social--zippy share share--centered article-cover__share\" data-glue-expansion-panel-expand-tooltip=\"Share: Expand to see social channels\" data-glue-expansion-panel-collapse-tooltip=\"Share: Hide social channels\" id=\"share-9b9d6347-d7bb-4df5-80a2-da3ca3e6d3b1\">\n<\/section><\/div>\n<picture class=\"article-cover__image\"><source media=\"(min-width: 1024px)\" type=\"image\/webp\" width=\"1072\" height=\"603\" srcset=\"https:\/\/lh3.googleusercontent.com\/4dhv1W6CjIsT923zvxVuO2VMDMZs3LpCzLhrqHjgLe7hzoQBkfdQyY1gh4RU5RbH47hBdkTZPjeNBb5ujEOMuZTsLSom3vWWyiCK_pcn2L0VEVSx=w1072-h603-n-nu-rw 1x, https:\/\/lh3.googleusercontent.com\/4dhv1W6CjIsT923zvxVuO2VMDMZs3LpCzLhrqHjgLe7hzoQBkfdQyY1gh4RU5RbH47hBdkTZPjeNBb5ujEOMuZTsLSom3vWWyiCK_pcn2L0VEVSx=w2144-h1206-n-nu-rw 2x\"\/><source media=\"(min-width: 600px)\" type=\"image\/webp\" width=\"928\" height=\"522\" srcset=\"https:\/\/lh3.googleusercontent.com\/4dhv1W6CjIsT923zvxVuO2VMDMZs3LpCzLhrqHjgLe7hzoQBkfdQyY1gh4RU5RbH47hBdkTZPjeNBb5ujEOMuZTsLSom3vWWyiCK_pcn2L0VEVSx=w928-h522-n-nu-rw 1x, https:\/\/lh3.googleusercontent.com\/4dhv1W6CjIsT923zvxVuO2VMDMZs3LpCzLhrqHjgLe7hzoQBkfdQyY1gh4RU5RbH47hBdkTZPjeNBb5ujEOMuZTsLSom3vWWyiCK_pcn2L0VEVSx=w1856-h1044-n-nu-rw 2x\"\/><source type=\"image\/webp\" width=\"528\" height=\"297\" srcset=\"https:\/\/lh3.googleusercontent.com\/4dhv1W6CjIsT923zvxVuO2VMDMZs3LpCzLhrqHjgLe7hzoQBkfdQyY1gh4RU5RbH47hBdkTZPjeNBb5ujEOMuZTsLSom3vWWyiCK_pcn2L0VEVSx=w528-h297-n-nu-rw 1x, https:\/\/lh3.googleusercontent.com\/4dhv1W6CjIsT923zvxVuO2VMDMZs3LpCzLhrqHjgLe7hzoQBkfdQyY1gh4RU5RbH47hBdkTZPjeNBb5ujEOMuZTsLSom3vWWyiCK_pcn2L0VEVSx=w1056-h594-n-nu-rw 2x\"\/><img fetchpriority=\"high\" decoding=\"async\" alt=\"\" height=\"603\" src=\"https:\/\/lh3.googleusercontent.com\/4dhv1W6CjIsT923zvxVuO2VMDMZs3LpCzLhrqHjgLe7hzoQBkfdQyY1gh4RU5RbH47hBdkTZPjeNBb5ujEOMuZTsLSom3vWWyiCK_pcn2L0VEVSx=w1072-h603-n-nu\" width=\"1072\"\/>\n    <\/picture>\n<\/p><\/div>\n<div class=\"gdm-rich-text rich-text\">\n<p data-block-key=\"9jxiq\"><b>AI system helps researchers piece together one of the largest molecular structures in human cells<\/b><\/p>\n<p data-block-key=\"1j49d\">When Pietro Fontana joined the Wu Lab at Harvard Medical School and Boston Children\u2019s Hospital in May 2019, he had before him what has been called one of the world\u2019s hardest, giant jigsaw puzzles. It was the task of piecing together a model of the nuclear pore complex, one of the largest molecular machines in human cells.<\/p>\n<p data-block-key=\"b6550\">\u201cIt was very challenging from the start,\u201d he explains. The complex has been called a <a href=\"https:\/\/www.nature.com\/articles\/d41586-022-00997-5\" rel=\"noopener\" target=\"_blank\">behemoth<\/a> for good reason: it is made up of more than 30 different protein subunits, termed nucleoporins, and in total contains more than 1,000 of them, intricately weaved together.<\/p>\n<\/div>\n<figure class=\"quote quote--inline\">\n<blockquote class=\"quote__text\">\n<p data-block-key=\"5mxht\">I think AlphaFold has completely changed the idea of structural biology<\/p>\n<\/blockquote><figcaption class=\"quote__author\">\n<p data-block-key=\"zv2uv\">Pietro Fontana, Postdoctoral Fellow<\/p>\n<\/figcaption><\/figure>\n<div class=\"gdm-rich-text rich-text\">\n<p data-block-key=\"9jxiq\">So when he sat down to use AlphaFold in his work for the first time two years later \u2013 together with Alexander Tong of University of California, Berkeley, who was more familiar with the AI system \u2013 he was uncertain if it would help. But what followed in the summer of 2021 was a somewhat unexpected breakthrough moment. AlphaFold predicted the structures of nucleoporins that had not been previously determined, unveiling more of the nuclear pore complex in the process. Thanks to the AI they could generate a near-complete model of the complex\u2019s cytoplasmic ring.<\/p>\n<\/div>\n<figure class=\"single-media single-media--large\"><figcaption class=\"single-media__caption\">\n<p data-block-key=\"t5iag\">Model of the nuclear pore complex cytoplasmic ring. Credit: Fontana et al. Science 2022<\/p>\n<\/figcaption><\/figure>\n<div class=\"gdm-rich-text rich-text\">\n<p data-block-key=\"qg00v\">\u201cMany components were already well known, but with AlphaFold, we also built the ones that were structurally unknown,\u201d he says. \u201cI started to realize how it\u2019s actually a big and useful tool for us. I think AlphaFold has completely changed the idea of structural biology.\u201d<\/p>\n<p data-block-key=\"d06li\">Molecular scientists like Fontana have dedicated themselves to deciphering the nuclear pore complex for decades. It is important because it is a gatekeeper for everything that goes in and out of the nucleus and is thought to hold answers to <a href=\"https:\/\/www.science.org\/doi\/10.1126\/science.abm9326\" rel=\"noopener\" target=\"_blank\">a growing number of serious human diseases<\/a>, including <a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8835831\/\" rel=\"noopener\" target=\"_blank\">amyotrophic lateral sclerosis (ALS) and other neurodegenerative illnesses<\/a>. Knowing how the complex is assembled could open the door to other groundbreaking, even life-saving, discoveries.<\/p>\n<\/div>\n<figure class=\"single-media single-media--inline\">\n<\/figure>\n<div class=\"gdm-rich-text rich-text\">\n<p data-block-key=\"qg00v\">The sheer size complex alone is challenging enough, but its many varied parts represent an added complication. \u201cThat\u2019s one major difficulty in achieving a resolution [clear enough] that we can interpret the sequence and structure of the complex,\u201d says Hao Wu, the lab\u2019s principal investigator. Even with a lot of data, the team had previously only managed structural images of medium resolution.<\/p>\n<p data-block-key=\"2643d\">Missing pieces of the puzzle also stymied progress. Without the full set, it is hard to tell how the jigsaw fits, says Wu. \u201cTo figure out how the different protein subunits come together, you really need to have some assistance on their individual structures,\u201d Wu explains.<\/p>\n<p data-block-key=\"7ipnh\">This is where AlphaFold changed the game for the Wu Lab which also included Ying Dong and Xiong Pi. Running it on proteins found in the eggs of the African clawed frog (Xenopus laevis) \u2013 used as a model system \u2013 the team, managed to map all the different subunit structures, which were unknown up until then. \u201cWhen we started trying, we didn\u2019t really know if the predictions would fit the map nicely,\u201d Wu recalls. \u201cBut that\u2019s what happened. That was pretty remarkable.\u201d<\/p>\n<p data-block-key=\"5krfo\">Of course, science is a collaborative effort. When it comes to solving a riddle as intricate as the nuclear pore complex, it\u2019s not just teamwork, but the culmination of the diligence and tenacity <a href=\"https:\/\/www.science.org\/doi\/10.1126\/science.abq4792\" rel=\"noopener\" target=\"_blank\">of many teams around the world.<\/a> Across the Atlantic, scientists from Max Planck Institute of Biophysics (MPIBP) and European Molecular Biology Laboratory (EMBL) in Germany have used AlphaFold in combination with cryo-electron tomography to model the human NPC. What they have achieved so far is a <a href=\"https:\/\/www.biorxiv.org\/content\/10.1101\/2021.10.26.465776v1\" rel=\"noopener\" target=\"_blank\">new model<\/a> twice as complete as the old one. Now covering two-thirds of the NPC, a huge part of the puzzle has been solved, and a big step has been taken towards understanding how it controls what goes in and out of the cell nucleus.<\/p>\n<\/div>\n<figure class=\"single-media single-media--fullbleed\"><figcaption class=\"single-media__caption\">\n<p data-block-key=\"vxulv\">The model of the human nuclear pore complex by scientists from MPIBP and EMBL in Germany. Credit: Agnieszka Obarska-Kosinska<\/p>\n<\/figcaption><\/figure>\n<div class=\"gdm-rich-text rich-text\">\n<p data-block-key=\"qg00v\">There is still a way to go \u2013 the final third remains. And while AlphaFold will make the remaining puzzle easier to solve, scientists are also aware of its limitations. According to Wu, the AI system worked well in the case of the nuclear pore complex because its subunits contained repeated helical structures, which tend to be easier to predict. But it might not be as straightforward for other proteins.<\/p>\n<p data-block-key=\"aqi3d\">It is important not to treat AlphaFold \u2013 nor any other AI tool for that matter \u2013 as a be-all and end-all. Tong. \u201cIn fact, AlphaFold can give you some very strange results,\u201d says Wu. \u201cBut if you understand how it predicts, you can take that into account [in the analysis].\u201d<\/p>\n<p data-block-key=\"51q1q\">Still, it\u2019s clear AlphaFold has not only expanded the limits of science, but also done it in a timeframe previously thought impossible. \u201cI\u2019m glad AlphaFold came out at the right moment because it sped everything up significantly,\u201d says Fontana.<\/p>\n<p data-block-key=\"b02nc\"><i>Fontana P., Dong Y., Pi X., Tong A.B., Hecksel C.W., Wang L., Fu TM., Bustamante C., Wu H. Structure of cytoplasmic ring of nuclear pore complex by integrative cryo-EM and AlphaFold. Science 376, 6598, (2022). DOI:10.1126\/science.abm9326.<\/i><\/p>\n<\/div>\n<aside class=\"related-posts\">\n<\/aside><\/div>\n<p>[ad_2]<br \/>\n<br \/><a href=\"https:\/\/deepmind.google\/discover\/blog\/alphafold-unlocks-one-of-the-greatest-puzzles-in-biology\/\">Source link <\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>[ad_1] Impact Published 28 July 2022 AI system helps researchers piece together one of the largest molecular structures<\/p>\n","protected":false},"author":2,"featured_media":765,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[21],"tags":[],"class_list":["post-812","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-deepmind-ai"],"featured_image_urls":{"full":["https:\/\/todaysainews.com\/wp-content\/uploads\/2023\/10\/E2UU4A-zCZ9b_oZyE_xQIeAZpDbjpcmw99-QVYVXs81UpJKnBzTo4O81rWapIqIfOAr39WSFMo336ekSH4_Z25BHiDamvwtQEKlSteg260fZhCwJw1200-h630-n-nu.jpeg",1200,630,false],"thumbnail":["https:\/\/todaysainews.com\/wp-content\/uploads\/2023\/10\/E2UU4A-zCZ9b_oZyE_xQIeAZpDbjpcmw99-QVYVXs81UpJKnBzTo4O81rWapIqIfOAr39WSFMo336ekSH4_Z25BHiDamvwtQEKlSteg260fZhCwJw1200-h630-n-nu-150x150.jpeg",150,150,true],"medium":["https:\/\/todaysainews.com\/wp-content\/uploads\/2023\/10\/E2UU4A-zCZ9b_oZyE_xQIeAZpDbjpcmw99-QVYVXs81UpJKnBzTo4O81rWapIqIfOAr39WSFMo336ekSH4_Z25BHiDamvwtQEKlSteg260fZhCwJw1200-h630-n-nu-300x158.jpeg",300,158,true],"medium_large":["https:\/\/todaysainews.com\/wp-content\/uploads\/2023\/10\/E2UU4A-zCZ9b_oZyE_xQIeAZpDbjpcmw99-QVYVXs81UpJKnBzTo4O81rWapIqIfOAr39WSFMo336ekSH4_Z25BHiDamvwtQEKlSteg260fZhCwJw1200-h630-n-nu-768x403.jpeg",640,336,true],"large":["https:\/\/todaysainews.com\/wp-content\/uploads\/2023\/10\/E2UU4A-zCZ9b_oZyE_xQIeAZpDbjpcmw99-QVYVXs81UpJKnBzTo4O81rWapIqIfOAr39WSFMo336ekSH4_Z25BHiDamvwtQEKlSteg260fZhCwJw1200-h630-n-nu-1024x538.jpeg",640,336,true],"1536x1536":["https:\/\/todaysainews.com\/wp-content\/uploads\/2023\/10\/E2UU4A-zCZ9b_oZyE_xQIeAZpDbjpcmw99-QVYVXs81UpJKnBzTo4O81rWapIqIfOAr39WSFMo336ekSH4_Z25BHiDamvwtQEKlSteg260fZhCwJw1200-h630-n-nu.jpeg",1200,630,false],"2048x2048":["https:\/\/todaysainews.com\/wp-content\/uploads\/2023\/10\/E2UU4A-zCZ9b_oZyE_xQIeAZpDbjpcmw99-QVYVXs81UpJKnBzTo4O81rWapIqIfOAr39WSFMo336ekSH4_Z25BHiDamvwtQEKlSteg260fZhCwJw1200-h630-n-nu.jpeg",1200,630,false],"broadnews-featured":["https:\/\/todaysainews.com\/wp-content\/uploads\/2023\/10\/E2UU4A-zCZ9b_oZyE_xQIeAZpDbjpcmw99-QVYVXs81UpJKnBzTo4O81rWapIqIfOAr39WSFMo336ekSH4_Z25BHiDamvwtQEKlSteg260fZhCwJw1200-h630-n-nu-1024x538.jpeg",1024,538,true],"broadnews-large":["https:\/\/todaysainews.com\/wp-content\/uploads\/2023\/10\/E2UU4A-zCZ9b_oZyE_xQIeAZpDbjpcmw99-QVYVXs81UpJKnBzTo4O81rWapIqIfOAr39WSFMo336ekSH4_Z25BHiDamvwtQEKlSteg260fZhCwJw1200-h630-n-nu-825x575.jpeg",825,575,true],"broadnews-medium":["https:\/\/todaysainews.com\/wp-content\/uploads\/2023\/10\/E2UU4A-zCZ9b_oZyE_xQIeAZpDbjpcmw99-QVYVXs81UpJKnBzTo4O81rWapIqIfOAr39WSFMo336ekSH4_Z25BHiDamvwtQEKlSteg260fZhCwJw1200-h630-n-nu-590x410.jpeg",590,410,true]},"author_info":{"info":["Sanna"]},"category_info":"<a href=\"https:\/\/todaysainews.com\/index.php\/category\/deepmind-ai\/\" rel=\"category tag\">DeepMind AI<\/a>","tag_info":"DeepMind AI","comment_count":"0","_links":{"self":[{"href":"https:\/\/todaysainews.com\/index.php\/wp-json\/wp\/v2\/posts\/812","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/todaysainews.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/todaysainews.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/todaysainews.com\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/todaysainews.com\/index.php\/wp-json\/wp\/v2\/comments?post=812"}],"version-history":[{"count":1,"href":"https:\/\/todaysainews.com\/index.php\/wp-json\/wp\/v2\/posts\/812\/revisions"}],"predecessor-version":[{"id":2661,"href":"https:\/\/todaysainews.com\/index.php\/wp-json\/wp\/v2\/posts\/812\/revisions\/2661"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/todaysainews.com\/index.php\/wp-json\/wp\/v2\/media\/765"}],"wp:attachment":[{"href":"https:\/\/todaysainews.com\/index.php\/wp-json\/wp\/v2\/media?parent=812"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/todaysainews.com\/index.php\/wp-json\/wp\/v2\/categories?post=812"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/todaysainews.com\/index.php\/wp-json\/wp\/v2\/tags?post=812"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}