Loading…

Strong and weak hydrogen bonds in the protein-ligand interface

The characteristics of NH···O, OH···O, and CH···O hydrogen bonds and other weak intermolecular interactions are analyzed in a large and diverse group of 251 protein–ligand complexes using a new computer program that was developed in‐house for this purpose. The interactions examined in the present...

Full description

Saved in:
Bibliographic Details
Published in:Proteins, structure, function, and bioinformatics structure, function, and bioinformatics, 2007-04, Vol.67 (1), p.128-141
Main Authors: Panigrahi, Sunil K., Desiraju, Gautam R.
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c4313-9902bd0ea911c611745c6183b5e3406e0e8c7c1b7403a290105773879ac7024f3
cites cdi_FETCH-LOGICAL-c4313-9902bd0ea911c611745c6183b5e3406e0e8c7c1b7403a290105773879ac7024f3
container_end_page 141
container_issue 1
container_start_page 128
container_title Proteins, structure, function, and bioinformatics
container_volume 67
creator Panigrahi, Sunil K.
Desiraju, Gautam R.
description The characteristics of NH···O, OH···O, and CH···O hydrogen bonds and other weak intermolecular interactions are analyzed in a large and diverse group of 251 protein–ligand complexes using a new computer program that was developed in‐house for this purpose. The interactions examined in the present study are those which occur in the active sites, defined here as a sphere of 10 Å radius around the ligand. Notably, NH···O and OH···O bonds tend towards linearity. Multifurcated interactions are especially common, especially multifurcated acceptors, and the average degree of furcation is 2.6 hydrogen bonds per furcated acceptor. A significant aspect of this study is that we have been able to assess the reliability of hydrogen bond geometry as a function of crystallographic resolution. Thresholds of 2.3 and 2.0 Å are established for strong and weak hydrogen bonds, below which hydrogen bond geometries may be safely considered for detailed analysis. Interactions involving water as donor or acceptor, and CH···O bonds with Gly and Tyr as donors are ubiquitous in the active site. A similar trend was observed in an external test set of 233 protein–ligand complexes belonging to the kinase family. Weaker interactions like XH···π (X = C, N, O) and those involving halogen atoms as electrophiles or nucleophiles have also been studied. We conclude that the strong and weak hydrogen bonds are ubiquitous in protein–ligand recognition, and that with suitable computational tools very large numbers of strong and weak intermolecular interactions in the ligand–protein interface may be analyzed reliably. Results confirm earlier trends reported previously by us but the extended nature of the present data set mean that the observed trends are more reliable. Proteins 2007. © 2007 Wiley‐Liss, Inc.
doi_str_mv 10.1002/prot.21253
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70459660</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>70459660</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4313-9902bd0ea911c611745c6183b5e3406e0e8c7c1b7403a290105773879ac7024f3</originalsourceid><addsrcrecordid>eNp9kMFOwkAQhjdGI4hefADTkweT4my3u9teTAwqmhBBxZhw2WzbASqlxd0S5O1tLerN03_55puZn5BTCl0K4F2uTFF2PepxtkfaFELpAmX-PmlDEEiX8YC3yJG17wAgQiYOSYtKD4Tgok2uXkpT5DNH54mzQb1w5tvEFDPMnajIE-ukuVPO0alXYJq7WTqryTQv0Ux1jMfkYKoziye77JDXu9tx794dDPsPveuBG_uMMjcMwYsSQB1SGgtKpc-rCFjEkfkgEDCIZUwj6QPTXggUuJQskKGOJXj-lHXIeeOtDvlYoy3VMrUxZpnOsVhbJcHnoRBQgRcNGJvCWoNTtTLpUputoqDqtlT9ivpuq4LPdtZ1tMTkD93VUwG0ATZphtt_VGr0PBz_SN1mJrUlfv7OaLNQQjLJ1dtjX7FJf3IDI6Ge2BesXIJB</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70459660</pqid></control><display><type>article</type><title>Strong and weak hydrogen bonds in the protein-ligand interface</title><source>Wiley</source><creator>Panigrahi, Sunil K. ; Desiraju, Gautam R.</creator><creatorcontrib>Panigrahi, Sunil K. ; Desiraju, Gautam R.</creatorcontrib><description>The characteristics of NH···O, OH···O, and CH···O hydrogen bonds and other weak intermolecular interactions are analyzed in a large and diverse group of 251 protein–ligand complexes using a new computer program that was developed in‐house for this purpose. The interactions examined in the present study are those which occur in the active sites, defined here as a sphere of 10 Å radius around the ligand. Notably, NH···O and OH···O bonds tend towards linearity. Multifurcated interactions are especially common, especially multifurcated acceptors, and the average degree of furcation is 2.6 hydrogen bonds per furcated acceptor. A significant aspect of this study is that we have been able to assess the reliability of hydrogen bond geometry as a function of crystallographic resolution. Thresholds of 2.3 and 2.0 Å are established for strong and weak hydrogen bonds, below which hydrogen bond geometries may be safely considered for detailed analysis. Interactions involving water as donor or acceptor, and CH···O bonds with Gly and Tyr as donors are ubiquitous in the active site. A similar trend was observed in an external test set of 233 protein–ligand complexes belonging to the kinase family. Weaker interactions like XH···π (X = C, N, O) and those involving halogen atoms as electrophiles or nucleophiles have also been studied. We conclude that the strong and weak hydrogen bonds are ubiquitous in protein–ligand recognition, and that with suitable computational tools very large numbers of strong and weak intermolecular interactions in the ligand–protein interface may be analyzed reliably. Results confirm earlier trends reported previously by us but the extended nature of the present data set mean that the observed trends are more reliable. Proteins 2007. © 2007 Wiley‐Liss, Inc.</description><identifier>ISSN: 0887-3585</identifier><identifier>EISSN: 1097-0134</identifier><identifier>DOI: 10.1002/prot.21253</identifier><identifier>PMID: 17206656</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Binding Sites ; Crystallography, X-Ray ; Databases, Protein ; force field ; Halogens - chemistry ; hydrogen bond ; Hydrogen Bonding ; interaction ; Ligands ; Phosphotransferases - chemistry ; protein data bank ; Proteins - chemistry ; Software ; water</subject><ispartof>Proteins, structure, function, and bioinformatics, 2007-04, Vol.67 (1), p.128-141</ispartof><rights>Copyright © 2007 Wiley‐Liss, Inc.</rights><rights>(c) 2007 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4313-9902bd0ea911c611745c6183b5e3406e0e8c7c1b7403a290105773879ac7024f3</citedby><cites>FETCH-LOGICAL-c4313-9902bd0ea911c611745c6183b5e3406e0e8c7c1b7403a290105773879ac7024f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17206656$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Panigrahi, Sunil K.</creatorcontrib><creatorcontrib>Desiraju, Gautam R.</creatorcontrib><title>Strong and weak hydrogen bonds in the protein-ligand interface</title><title>Proteins, structure, function, and bioinformatics</title><addtitle>Proteins</addtitle><description>The characteristics of NH···O, OH···O, and CH···O hydrogen bonds and other weak intermolecular interactions are analyzed in a large and diverse group of 251 protein–ligand complexes using a new computer program that was developed in‐house for this purpose. The interactions examined in the present study are those which occur in the active sites, defined here as a sphere of 10 Å radius around the ligand. Notably, NH···O and OH···O bonds tend towards linearity. Multifurcated interactions are especially common, especially multifurcated acceptors, and the average degree of furcation is 2.6 hydrogen bonds per furcated acceptor. A significant aspect of this study is that we have been able to assess the reliability of hydrogen bond geometry as a function of crystallographic resolution. Thresholds of 2.3 and 2.0 Å are established for strong and weak hydrogen bonds, below which hydrogen bond geometries may be safely considered for detailed analysis. Interactions involving water as donor or acceptor, and CH···O bonds with Gly and Tyr as donors are ubiquitous in the active site. A similar trend was observed in an external test set of 233 protein–ligand complexes belonging to the kinase family. Weaker interactions like XH···π (X = C, N, O) and those involving halogen atoms as electrophiles or nucleophiles have also been studied. We conclude that the strong and weak hydrogen bonds are ubiquitous in protein–ligand recognition, and that with suitable computational tools very large numbers of strong and weak intermolecular interactions in the ligand–protein interface may be analyzed reliably. Results confirm earlier trends reported previously by us but the extended nature of the present data set mean that the observed trends are more reliable. Proteins 2007. © 2007 Wiley‐Liss, Inc.</description><subject>Binding Sites</subject><subject>Crystallography, X-Ray</subject><subject>Databases, Protein</subject><subject>force field</subject><subject>Halogens - chemistry</subject><subject>hydrogen bond</subject><subject>Hydrogen Bonding</subject><subject>interaction</subject><subject>Ligands</subject><subject>Phosphotransferases - chemistry</subject><subject>protein data bank</subject><subject>Proteins - chemistry</subject><subject>Software</subject><subject>water</subject><issn>0887-3585</issn><issn>1097-0134</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><recordid>eNp9kMFOwkAQhjdGI4hefADTkweT4my3u9teTAwqmhBBxZhw2WzbASqlxd0S5O1tLerN03_55puZn5BTCl0K4F2uTFF2PepxtkfaFELpAmX-PmlDEEiX8YC3yJG17wAgQiYOSYtKD4Tgok2uXkpT5DNH54mzQb1w5tvEFDPMnajIE-ukuVPO0alXYJq7WTqryTQv0Ux1jMfkYKoziye77JDXu9tx794dDPsPveuBG_uMMjcMwYsSQB1SGgtKpc-rCFjEkfkgEDCIZUwj6QPTXggUuJQskKGOJXj-lHXIeeOtDvlYoy3VMrUxZpnOsVhbJcHnoRBQgRcNGJvCWoNTtTLpUputoqDqtlT9ivpuq4LPdtZ1tMTkD93VUwG0ATZphtt_VGr0PBz_SN1mJrUlfv7OaLNQQjLJ1dtjX7FJf3IDI6Ge2BesXIJB</recordid><startdate>200704</startdate><enddate>200704</enddate><creator>Panigrahi, Sunil K.</creator><creator>Desiraju, Gautam R.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200704</creationdate><title>Strong and weak hydrogen bonds in the protein-ligand interface</title><author>Panigrahi, Sunil K. ; Desiraju, Gautam R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4313-9902bd0ea911c611745c6183b5e3406e0e8c7c1b7403a290105773879ac7024f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Binding Sites</topic><topic>Crystallography, X-Ray</topic><topic>Databases, Protein</topic><topic>force field</topic><topic>Halogens - chemistry</topic><topic>hydrogen bond</topic><topic>Hydrogen Bonding</topic><topic>interaction</topic><topic>Ligands</topic><topic>Phosphotransferases - chemistry</topic><topic>protein data bank</topic><topic>Proteins - chemistry</topic><topic>Software</topic><topic>water</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Panigrahi, Sunil K.</creatorcontrib><creatorcontrib>Desiraju, Gautam R.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Proteins, structure, function, and bioinformatics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Panigrahi, Sunil K.</au><au>Desiraju, Gautam R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Strong and weak hydrogen bonds in the protein-ligand interface</atitle><jtitle>Proteins, structure, function, and bioinformatics</jtitle><addtitle>Proteins</addtitle><date>2007-04</date><risdate>2007</risdate><volume>67</volume><issue>1</issue><spage>128</spage><epage>141</epage><pages>128-141</pages><issn>0887-3585</issn><eissn>1097-0134</eissn><abstract>The characteristics of NH···O, OH···O, and CH···O hydrogen bonds and other weak intermolecular interactions are analyzed in a large and diverse group of 251 protein–ligand complexes using a new computer program that was developed in‐house for this purpose. The interactions examined in the present study are those which occur in the active sites, defined here as a sphere of 10 Å radius around the ligand. Notably, NH···O and OH···O bonds tend towards linearity. Multifurcated interactions are especially common, especially multifurcated acceptors, and the average degree of furcation is 2.6 hydrogen bonds per furcated acceptor. A significant aspect of this study is that we have been able to assess the reliability of hydrogen bond geometry as a function of crystallographic resolution. Thresholds of 2.3 and 2.0 Å are established for strong and weak hydrogen bonds, below which hydrogen bond geometries may be safely considered for detailed analysis. Interactions involving water as donor or acceptor, and CH···O bonds with Gly and Tyr as donors are ubiquitous in the active site. A similar trend was observed in an external test set of 233 protein–ligand complexes belonging to the kinase family. Weaker interactions like XH···π (X = C, N, O) and those involving halogen atoms as electrophiles or nucleophiles have also been studied. We conclude that the strong and weak hydrogen bonds are ubiquitous in protein–ligand recognition, and that with suitable computational tools very large numbers of strong and weak intermolecular interactions in the ligand–protein interface may be analyzed reliably. Results confirm earlier trends reported previously by us but the extended nature of the present data set mean that the observed trends are more reliable. Proteins 2007. © 2007 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>17206656</pmid><doi>10.1002/prot.21253</doi><tpages>14</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0887-3585
ispartof Proteins, structure, function, and bioinformatics, 2007-04, Vol.67 (1), p.128-141
issn 0887-3585
1097-0134
language eng
recordid cdi_proquest_miscellaneous_70459660
source Wiley
subjects Binding Sites
Crystallography, X-Ray
Databases, Protein
force field
Halogens - chemistry
hydrogen bond
Hydrogen Bonding
interaction
Ligands
Phosphotransferases - chemistry
protein data bank
Proteins - chemistry
Software
water
title Strong and weak hydrogen bonds in the protein-ligand interface
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T20%3A37%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Strong%20and%20weak%20hydrogen%20bonds%20in%20the%20protein-ligand%20interface&rft.jtitle=Proteins,%20structure,%20function,%20and%20bioinformatics&rft.au=Panigrahi,%20Sunil%20K.&rft.date=2007-04&rft.volume=67&rft.issue=1&rft.spage=128&rft.epage=141&rft.pages=128-141&rft.issn=0887-3585&rft.eissn=1097-0134&rft_id=info:doi/10.1002/prot.21253&rft_dat=%3Cproquest_cross%3E70459660%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c4313-9902bd0ea911c611745c6183b5e3406e0e8c7c1b7403a290105773879ac7024f3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=70459660&rft_id=info:pmid/17206656&rfr_iscdi=true