{"id":1578,"date":"2024-05-15T11:13:00","date_gmt":"2024-05-15T03:13:00","guid":{"rendered":"https:\/\/aimedorig.com\/wordpress\/?p=1578"},"modified":"2024-05-28T19:16:34","modified_gmt":"2024-05-28T11:16:34","slug":"gpd%e5%85%a8%e6%96%b0%e8%9b%8b%e7%99%bd%e5%ba%8f%e5%88%97%e8%ae%be%e8%ae%a1%e6%96%b9%e6%b3%95-ai%e8%b5%8b%e8%83%bd%e8%9b%8b%e7%99%bd%e8%b4%a8%e8%8d%af%e7%89%a9%e5%8f%91%e7%8e%b0-%e8%8b%b1%e6%96%87","status":"publish","type":"post","link":"https:\/\/aimedorig.com\/wordpress\/?p=1578&lang=en","title":{"rendered":"GPD New Protein Sequence Design Method | AI Empowered Protein Drug Discovery"},"content":{"rendered":"\t\t<div data-elementor-type=\"wp-post\" data-elementor-id=\"1578\" class=\"elementor elementor-1578\">\n\t\t\t\t<div class=\"elementor-element elementor-element-34c16b25 e-flex e-con-boxed e-con e-parent\" data-id=\"34c16b25\" data-element_type=\"container\">\n\t\t\t\t\t<div class=\"e-con-inner\">\n\t\t\t\t<div class=\"elementor-element elementor-element-3295d2d7 elementor-widget elementor-widget-text-editor\" data-id=\"3295d2d7\" data-element_type=\"widget\" data-widget_type=\"text-editor.default\">\n\t\t\t\t<div class=\"elementor-widget-container\">\n\t\t\t<style>\/*! elementor - v3.23.0 - 25-07-2024 *\/\n.elementor-widget-text-editor.elementor-drop-cap-view-stacked .elementor-drop-cap{background-color:#69727d;color:#fff}.elementor-widget-text-editor.elementor-drop-cap-view-framed .elementor-drop-cap{color:#69727d;border:3px solid;background-color:transparent}.elementor-widget-text-editor:not(.elementor-drop-cap-view-default) .elementor-drop-cap{margin-top:8px}.elementor-widget-text-editor:not(.elementor-drop-cap-view-default) .elementor-drop-cap-letter{width:1em;height:1em}.elementor-widget-text-editor .elementor-drop-cap{float:left;text-align:center;line-height:1;font-size:50px}.elementor-widget-text-editor .elementor-drop-cap-letter{display:inline-block}<\/style>\t\t\t\t<!-- wp:paragraph -->\n<p>Recently, Professor Haifeng Chen, co-founder of company, developed an innovative and efficient new protein sequence design method called GPD. Compared to the current state-of-the-art method, proteinMPNN, GPD exhibits significantly higher sequence diversity and generates sequences 2.2 times faster, greatly enhancing the de novo design capabilities of industrial enzymes and protein drugs. The research results were published in the CAS top journal &#8220;Briefings in Bioinformatics.&#8221;<\/p>\n<!-- \/wp:paragraph --><!-- wp:image {\"id\":1264,\"sizeSlug\":\"full\",\"linkDestination\":\"none\"} -->\n<figure class=\"wp-block-image size-full\"><img fetchpriority=\"high\" decoding=\"async\" width=\"865\" height=\"254\" class=\"wp-image-1264\" src=\"https:\/\/aimedorig.com\/wordpress\/wp-content\/uploads\/2024\/05\/image-3.png\" alt=\"\" srcset=\"https:\/\/aimedorig.com\/wordpress\/wp-content\/uploads\/2024\/05\/image-3.png 865w, https:\/\/aimedorig.com\/wordpress\/wp-content\/uploads\/2024\/05\/image-3-300x88.png 300w, https:\/\/aimedorig.com\/wordpress\/wp-content\/uploads\/2024\/05\/image-3-768x226.png 768w\" sizes=\"(max-width: 865px) 100vw, 865px\" \/><\/figure>\n<!-- \/wp:image --><!-- wp:paragraph -->\n<figure class=\"wp-block-image size-full\">\n<p>Protein design is central to almost all protein engineering problems because it enables the creation of proteins with novel biological functions and can improve the catalytic efficiency of enzymes, among other benefits. A key issue in protein design is the fixed-backbone protein sequence design, which aims to design new sequences that conform to a predetermined protein backbone structure. However, existing sequence design methods have various limitations, such as low sequence diversity and insufficient experimental validation of the designed functional proteins, which severely hinder functional protein design.<\/p>\n<p>To address these limitations, the team developed the Graphormer-based Protein Design (GPD) model in this study. This model uses a Transformer to perform graph-based 3D protein structure representation, incorporating Gaussian noise and sequence random masking into node features, thereby enhancing the quality of sequence design.<\/p>\n<img decoding=\"async\" class=\"alignnone wp-image-1756 size-full\" src=\"https:\/\/aimedorig.com\/wordpress\/wp-content\/uploads\/2024\/05\/bc96bd44f1359e07043392f533955fe.png\" alt=\"\" width=\"1573\" height=\"1342\" srcset=\"https:\/\/aimedorig.com\/wordpress\/wp-content\/uploads\/2024\/05\/bc96bd44f1359e07043392f533955fe.png 1573w, https:\/\/aimedorig.com\/wordpress\/wp-content\/uploads\/2024\/05\/bc96bd44f1359e07043392f533955fe-300x256.png 300w, https:\/\/aimedorig.com\/wordpress\/wp-content\/uploads\/2024\/05\/bc96bd44f1359e07043392f533955fe-1024x874.png 1024w, https:\/\/aimedorig.com\/wordpress\/wp-content\/uploads\/2024\/05\/bc96bd44f1359e07043392f533955fe-768x655.png 768w, https:\/\/aimedorig.com\/wordpress\/wp-content\/uploads\/2024\/05\/bc96bd44f1359e07043392f533955fe-1536x1310.png 1536w\" sizes=\"(max-width: 1573px) 100vw, 1573px\" \/>\n<figcaption class=\"wp-element-caption\">Figure 1. GPD Model Architecture and Input Features<\/figcaption>\n<\/figure>\n<!-- \/wp:image --><!-- wp:paragraph -->\n<p>Subsequently, the team evaluated the sequence design quality of GPD during the research process and found that it could design and generate more reasonable protein sequences while maintaining high sequence diversity. Most of the designed sequences could also fold into the desired structures in structural prediction models. Overall, GPD outperformed existing models in terms of sequence foldability, sequence homology, and sequence diversity.<\/p>\n<!-- \/wp:paragraph --><!-- wp:image {\"id\":1267,\"sizeSlug\":\"full\",\"linkDestination\":\"none\"} -->\n<figure class=\"wp-block-image size-full\"><img decoding=\"async\" width=\"865\" height=\"559\" class=\"wp-image-1267\" src=\"https:\/\/aimedorig.com\/wordpress\/wp-content\/uploads\/2024\/05\/image-6.png\" alt=\"\" srcset=\"https:\/\/aimedorig.com\/wordpress\/wp-content\/uploads\/2024\/05\/image-6.png 865w, https:\/\/aimedorig.com\/wordpress\/wp-content\/uploads\/2024\/05\/image-6-300x194.png 300w, https:\/\/aimedorig.com\/wordpress\/wp-content\/uploads\/2024\/05\/image-6-768x496.png 768w\" sizes=\"(max-width: 865px) 100vw, 865px\" \/>\n<figcaption class=\"wp-element-caption\">Figure 2. Evaluation of GPD&#8217;s Sequence Design Quality<\/figcaption>\n<\/figure>\n<!-- \/wp:image --><!-- wp:paragraph -->\n<p>Additionally, Intelligent Medicine Original, in collaboration with Shanghai Jiao Tong University, applied GPD to the redesign of Antarctic yeast lipase (CALB), generating and screening nine artificially designed protein sequences. Compared to the wild-type CalB, one of the designed sequences exhibited a 1.7-fold increase in catalytic activity. The experimental results further demonstrate the rationality of GPD&#8217;s design, as well as its efficiency over previous rational design or directed evolution methods.<\/p>\n<p>Moreover, enzyme activity tests for multiple substrates revealed that the sequences designed by GPD exhibited high substrate specificity, showing strong substrate selectivity on p-nitrophenyl acetate with different carbon chain lengths (C2-C16). This has significant implications for the industrial application of CALB enzymes.<\/p>\n<p>Intelligent Medicine Original&#8217;s innovative protein sequence design method, GPD, can be used for the de novo design of industrial enzymes and protein drugs, providing a methodological foundation for the rapid development of new productive forces. The company aims to introduce advanced computational methods into the biopharmaceutical field, striving to create an AI-powered platform for protease modification and innovative drug design.<\/p>\n<!-- \/wp:paragraph -->\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t","protected":false},"excerpt":{"rendered":"<p>Recently, Professor Haifeng Chen, co-founder of company [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_eb_attr":"","footnotes":""},"categories":[85],"tags":[],"class_list":["post-1578","post","type-post","status-publish","format-standard","hentry","category-_eng"],"blocksy_meta":[],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/aimedorig.com\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1578"}],"collection":[{"href":"https:\/\/aimedorig.com\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/aimedorig.com\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/aimedorig.com\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/aimedorig.com\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1578"}],"version-history":[{"count":7,"href":"https:\/\/aimedorig.com\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1578\/revisions"}],"predecessor-version":[{"id":1760,"href":"https:\/\/aimedorig.com\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/1578\/revisions\/1760"}],"wp:attachment":[{"href":"https:\/\/aimedorig.com\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1578"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/aimedorig.com\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1578"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/aimedorig.com\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1578"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}