{"id":24483,"date":"2021-12-12T15:26:02","date_gmt":"2021-12-12T15:26:02","guid":{"rendered":"https:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=24483"},"modified":"2021-12-12T15:29:42","modified_gmt":"2021-12-12T15:29:42","slug":"protein-biotin-complexes-crystal-structure-mining","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24483","title":{"rendered":"Protein-Biotin complexes. Crystal structure mining."},"content":{"rendered":"
\n

In the previous post<\/a>, I showed some of the diverse “non-classical”interactions between Biotin and a protein where it binds very strongly. Here I take a look at two of these interactions to discover how common they are in small molecule structures.<\/p>\n

The first search is of a CH hydrogen bond to the face of the aromatic ring in a tryptophane residue<\/p>\n

\"\"<\/a> The search is shown below, in which the distance of the hydrogen to the ring centroid is defined, as is the angle subtended at that centroid, constrained to lie within 20\u00b0 of a vertical approach.<\/p>\n

\"\"<\/a><\/p>\n

The resulting heat plot shows 2772 entries (no disorder, no errors, R < 0.05), with a rather diffuse red spot at around 2.7-2.8\u00c5 (but which can be as short as 2.3\u00c5) and an angle of approach of ~90\u00b15\u00b0. This matches the concept of a region of interaction rather than a more focused “hydrogen bond”. It is seen as a relatively common motif!<\/p>\n

\"\"<\/a>
\n<\/a><\/p>\n

The next search is for “hydrogen bonding” between the sulfur of an C-S-C unit (as found in Biotin) and an OH group. \"\"<\/a>
\n<\/a> This is less common, with 151 entries in the Cambridge small molecule database, the red spot having a relatively short S…H distance of 1.65\u00c5 and a slightly non linear angle.<\/p>\n

\"\"<\/a><\/p>\n

The NH analogue of this search is shown below (422 hits) shows two clusters. The one with a large angle at H is more concentrated and reveals a distance of ~2.9\u00c5 whilst the second cluster has smaller angle and a long tail out to ~2.5\u00c5\"\"<\/a><\/p>\n

So we conclude there is ample evidence in small molecule crystal structures for the types of interaction mooted for Biotin with proteins.<\/p>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

In the previous post, I showed some of the diverse “non-classical”interactions between Biotin and a protein where it binds very strongly. Here I take a look at two of these interactions to discover how common they are in small molecule structures. The first search is of a CH hydrogen bond to the face of the […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"activitypub_content_warning":"","activitypub_content_visibility":"","activitypub_max_image_attachments":5,"activitypub_interaction_policy_quote":"anyone","activitypub_status":"","footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1745,4],"tags":[],"ppma_author":[2661],"class_list":["post-24483","post","type-post","status-publish","format-standard","hentry","category-crystal_structure_mining","category-interesting-chemistry"],"yoast_head":"\nProtein-Biotin complexes. Crystal structure mining. - Henry Rzepa's Blog<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24483\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Protein-Biotin complexes. Crystal structure mining. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"In the previous post, I showed some of the diverse “non-classical”interactions between Biotin and a protein where it binds very strongly. Here I take a look at two of these interactions to discover how common they are in small molecule structures. The first search is of a CH hydrogen bond to the face of the […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24483\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2021-12-12T15:26:02+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2021-12-12T15:29:42+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/12\/tryptophane.svg\" \/>\n<meta name=\"author\" content=\"Henry Rzepa\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Henry Rzepa\" \/>\n\t<meta name=\"twitter:label2\" content=\"Estimated reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"1 minute\" \/>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Protein-Biotin complexes. Crystal structure mining. - Henry Rzepa's Blog","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24483","og_locale":"en_GB","og_type":"article","og_title":"Protein-Biotin complexes. Crystal structure mining. - Henry Rzepa's Blog","og_description":"In the previous post, I showed some of the diverse “non-classical”interactions between Biotin and a protein where it binds very strongly. Here I take a look at two of these interactions to discover how common they are in small molecule structures. The first search is of a CH hydrogen bond to the face of the […]","og_url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24483","og_site_name":"Henry Rzepa's Blog","article_published_time":"2021-12-12T15:26:02+00:00","article_modified_time":"2021-12-12T15:29:42+00:00","og_image":[{"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2021\/12\/tryptophane.svg","type":"","width":"","height":""}],"author":"Henry Rzepa","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Henry Rzepa","Estimated reading time":"1 minute"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24483#article","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=24483"},"author":{"name":"Henry Rzepa","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"headline":"Protein-Biotin complexes. 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The author argues that an accumulation of both CH-\u03c0 and CH-O together with more classical hydrogen bonds\u2026","rel":"","context":"In "Interesting chemistry"","block_context":{"text":"Interesting chemistry","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=4"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":17579,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=17579","url_meta":{"origin":24483,"position":1},"title":"Ammonium tetraphenylborate and the mystery of its \u03c0-facial hydrogen bonding.","author":"Henry Rzepa","date":"March 10, 2017","format":false,"excerpt":"A few years back, I did a post about the Pirkle reagent and the unusual \u03c0-facial hydrogen bonding structure it exhibits. For the Pirkle reagent, this bonding manifests as a close contact between the acidic OH hydrogen and the edge of a phenyl ring; the hydrogen bond is off-centre from\u2026","rel":"","context":"In "crystal_structure_mining"","block_context":{"text":"crystal_structure_mining","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1745"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2017\/03\/142-1024x770.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":16573,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16573","url_meta":{"origin":24483,"position":2},"title":"How does an OH or NH group approach an aromatic ring to hydrogen bond with its \u03c0-face?","author":"Henry Rzepa","date":"June 22, 2016","format":false,"excerpt":"I previously used data mining of crystal structures to explore the directing influence of substituents on aromatic and heteroaromatic rings. Here\u00a0I explore, quite literally, a different angle to the hydrogen bonding interactions between a benzene ring and\u00a0OH or NH groups. I start by defining a benzene ring with a centroid.\u2026","rel":"","context":"In "Chemical IT"","block_context":{"text":"Chemical IT","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=2"},"img":{"alt_text":"aromatic-pi-query","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2016\/06\/aromatic-pi-query-1-e1466580253270.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":18165,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=18165","url_meta":{"origin":24483,"position":3},"title":"\u03c0-Facial hydrogen bonds to alkenes (revisited): how close can an acidic hydrogen approach?","author":"Henry Rzepa","date":"April 15, 2017","format":false,"excerpt":"Back in the early 1990s, we first discovered the delights of searching crystal structures\u00a0for unusual\u00a0bonding features. One of the first cases was a search for hydrogen bonds formed to the\u00a0\u03c0-faces of alkenes and alkynes. In those days the CSD database of crystal structures was a lot smaller (<80,000 structures; it's\u2026","rel":"","context":"In "crystal_structure_mining"","block_context":{"text":"crystal_structure_mining","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1745"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2017\/04\/SQ-H-pi-1024x783.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":15992,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=15992","url_meta":{"origin":24483,"position":4},"title":"Celebrating Paul Schleyer: searching for hidden treasures in the structures of metallocene complexes.","author":"Henry Rzepa","date":"April 2, 2016","format":false,"excerpt":"A celebration of the life and work of the great chemist\u00a0Paul von R. Schleyer was held this week in Erlangen, Germany. There were many fantastic talks given by some great chemists describing fascinating chemistry. Here I highlight the presentation\u00a0given by\u00a0Andy Streitwieser on the topic of organolithium chemistry, also a great\u2026","rel":"","context":"In "Chemical IT"","block_context":{"text":"Chemical IT","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=2"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":18399,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=18399","url_meta":{"origin":24483,"position":5},"title":"CH\u22c5\u22c5\u22c5\u03c0 Interactions between methyl and carbonyl groups in proteins: a small molecule check.","author":"Henry Rzepa","date":"May 29, 2017","format":false,"excerpt":"Derek Lowe highlights a recent article postulating\u00a0CH\u22c5\u22c5\u22c5\u03c0 interactions in proteins. Here I report a quick check using the small molecule crystal structure database (CSD). The search query (DOI:\u00a010.14469\/hpc\/2594)\u00a0is shown below. The distance refers to that between the (normalised) position of a hydrogen on a 4-coordinated carbon atom and the centroid\u2026","rel":"","context":"In "crystal_structure_mining"","block_context":{"text":"crystal_structure_mining","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1745"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2017\/05\/152-1024x637.jpg?resize=350%2C200","width":350,"height":200},"classes":[]}],"jetpack_likes_enabled":false,"authors":[{"term_id":2661,"user_id":1,"is_guest":0,"slug":"admin","display_name":"Henry Rzepa","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/897b6740f7f599bca7942cdf7d7914af5988937ae0e3869ab09aebb87f26a731?s=96&d=blank&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/24483","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=24483"}],"version-history":[{"count":10,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/24483\/revisions"}],"predecessor-version":[{"id":24502,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/24483\/revisions\/24502"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=24483"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=24483"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=24483"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=24483"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}