Gramicidin A Channel as a Test Ground for Molecular Dynamics Force Fields
We use the well-known structural and functional properties of the gramicidin A channel to test the appropriateness of force fields commonly used in molecular dynamics (MD) simulations of ion channels. For this purpose, the high-resolution structure of the gramicidin A dimer is embedded in a dimyrist...
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| Veröffentlicht in: | Biophysical journal 2003-04, Vol.84 (4), p.2159-2168 |
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| creator | Allen, Toby W. Baştuğ, Turgut Kuyucak, Serdar Chung, Shin-Ho |
| description | We use the well-known structural and functional properties of the gramicidin A channel to test the appropriateness of force fields commonly used in molecular dynamics (MD) simulations of ion channels. For this purpose, the high-resolution structure of the gramicidin A dimer is embedded in a dimyristoylphosphatidylcholine bilayer, and the potential of mean force of a K
+ ion is calculated along the channel axis using the umbrella sampling method. Calculations are performed using two of the most common force fields in MD simulations: CHARMM and GROMACS. Both force fields lead to large central barriers for K
+ ion permeation, that are substantially higher than those deduced from the physiological data by inverse methods. In long MD simulations lasting over 60
ns, several ions are observed to enter the binding site but none of them crossed the channel despite the presence of a large driving field. The present results, taken together with many earlier studies, highlights the shortcomings of the standard force fields used in MD simulations of ion channels and calls for construction of more appropriate force fields for this purpose. |
| doi_str_mv | 10.1016/S0006-3495(03)75022-X |
| format | Article |
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+ ion is calculated along the channel axis using the umbrella sampling method. Calculations are performed using two of the most common force fields in MD simulations: CHARMM and GROMACS. Both force fields lead to large central barriers for K
+ ion permeation, that are substantially higher than those deduced from the physiological data by inverse methods. In long MD simulations lasting over 60
ns, several ions are observed to enter the binding site but none of them crossed the channel despite the presence of a large driving field. The present results, taken together with many earlier studies, highlights the shortcomings of the standard force fields used in MD simulations of ion channels and calls for construction of more appropriate force fields for this purpose.</description><identifier>ISSN: 0006-3495</identifier><identifier>EISSN: 1542-0086</identifier><identifier>DOI: 10.1016/S0006-3495(03)75022-X</identifier><identifier>PMID: 12668425</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Binding Sites ; Biophysical Theory and Modeling ; Cell Membrane Permeability ; Computer Simulation ; Crystallography - methods ; Dimerization ; Dimyristoylphosphatidylcholine - chemistry ; Gramicidin - chemistry ; Ion Channel Gating ; Ion Channels - chemistry ; Ions ; Lipid Bilayers - chemistry ; Macromolecular Substances ; Models, Molecular ; Molecular Conformation ; Molecules ; Motion ; Neurotransmitters ; Quality Control ; Reproducibility of Results ; Sensitivity and Specificity ; Static Electricity ; Stress, Mechanical</subject><ispartof>Biophysical journal, 2003-04, Vol.84 (4), p.2159-2168</ispartof><rights>2003 The Biophysical Society</rights><rights>Copyright Biophysical Society Apr 2003</rights><rights>Copyright © 2003, Biophysical Society 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c556t-ef8c8550b2885317b6ad98768ff2791d49b5aee38d3c8ea61d2c0dd7b836b4fd3</citedby><cites>FETCH-LOGICAL-c556t-ef8c8550b2885317b6ad98768ff2791d49b5aee38d3c8ea61d2c0dd7b836b4fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1302783/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0006-3495(03)75022-X$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,3550,27924,27925,45995,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12668425$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Allen, Toby W.</creatorcontrib><creatorcontrib>Baştuğ, Turgut</creatorcontrib><creatorcontrib>Kuyucak, Serdar</creatorcontrib><creatorcontrib>Chung, Shin-Ho</creatorcontrib><title>Gramicidin A Channel as a Test Ground for Molecular Dynamics Force Fields</title><title>Biophysical journal</title><addtitle>Biophys J</addtitle><description>We use the well-known structural and functional properties of the gramicidin A channel to test the appropriateness of force fields commonly used in molecular dynamics (MD) simulations of ion channels. For this purpose, the high-resolution structure of the gramicidin A dimer is embedded in a dimyristoylphosphatidylcholine bilayer, and the potential of mean force of a K
+ ion is calculated along the channel axis using the umbrella sampling method. Calculations are performed using two of the most common force fields in MD simulations: CHARMM and GROMACS. Both force fields lead to large central barriers for K
+ ion permeation, that are substantially higher than those deduced from the physiological data by inverse methods. In long MD simulations lasting over 60
ns, several ions are observed to enter the binding site but none of them crossed the channel despite the presence of a large driving field. The present results, taken together with many earlier studies, highlights the shortcomings of the standard force fields used in MD simulations of ion channels and calls for construction of more appropriate force fields for this purpose.</description><subject>Binding Sites</subject><subject>Biophysical Theory and Modeling</subject><subject>Cell Membrane Permeability</subject><subject>Computer Simulation</subject><subject>Crystallography - methods</subject><subject>Dimerization</subject><subject>Dimyristoylphosphatidylcholine - chemistry</subject><subject>Gramicidin - chemistry</subject><subject>Ion Channel Gating</subject><subject>Ion Channels - chemistry</subject><subject>Ions</subject><subject>Lipid Bilayers - chemistry</subject><subject>Macromolecular Substances</subject><subject>Models, Molecular</subject><subject>Molecular Conformation</subject><subject>Molecules</subject><subject>Motion</subject><subject>Neurotransmitters</subject><subject>Quality Control</subject><subject>Reproducibility of Results</subject><subject>Sensitivity and Specificity</subject><subject>Static Electricity</subject><subject>Stress, Mechanical</subject><issn>0006-3495</issn><issn>1542-0086</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkcFPFDEUxhujkRX9EzCNByOHwdd22ulcNGRlVxIIBzDh1nTaN1Iy22K7Q8J_7yy7QfTiqYf3-77X732EHDA4YsDU50sAUJWoW_kJxGEjgfPq-gWZMVnzCkCrl2T2hOyRN6XcAjAugb0me4wrpWsuZ-R0me0quOBDpMd0fmNjxIHaQi29wrKmy5zG6GmfMj1PA7pxsJl-e4gbUaGLlB3SRcDBl7fkVW-Hgu927z75sTi5mn-vzi6Wp_Pjs8pJqdYV9tppKaHjWkvBmk5Z3-pG6b7nTct83XbSIgrthdNoFfPcgfdNp4Xq6t6LffJl63s3div0DuM628Hc5bCy-cEkG8zfkxhuzM90b5gA3mgxGXzcGeT0a5xCmlUoDofBRkxjMY1gteKwAT_8A96mMccpnOFMNiDamk-Q3EIup1Iy9k8_YWA2TZnHpsymBgPCPDZlrifd--cx_qh21UzA1y2A0zHvA2ZTXMDo0IeMbm18Cv9Z8RsnKqLa</recordid><startdate>20030401</startdate><enddate>20030401</enddate><creator>Allen, Toby W.</creator><creator>Baştuğ, Turgut</creator><creator>Kuyucak, Serdar</creator><creator>Chung, Shin-Ho</creator><general>Elsevier Inc</general><general>Biophysical Society</general><scope>6I.</scope><scope>AAFTH</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>3V.</scope><scope>7QO</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20030401</creationdate><title>Gramicidin A Channel as a Test Ground for Molecular Dynamics Force Fields</title><author>Allen, Toby W. ; Baştuğ, Turgut ; Kuyucak, Serdar ; Chung, Shin-Ho</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c556t-ef8c8550b2885317b6ad98768ff2791d49b5aee38d3c8ea61d2c0dd7b836b4fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Binding Sites</topic><topic>Biophysical Theory and Modeling</topic><topic>Cell Membrane Permeability</topic><topic>Computer Simulation</topic><topic>Crystallography - methods</topic><topic>Dimerization</topic><topic>Dimyristoylphosphatidylcholine - chemistry</topic><topic>Gramicidin - chemistry</topic><topic>Ion Channel Gating</topic><topic>Ion Channels - chemistry</topic><topic>Ions</topic><topic>Lipid Bilayers - chemistry</topic><topic>Macromolecular Substances</topic><topic>Models, Molecular</topic><topic>Molecular Conformation</topic><topic>Molecules</topic><topic>Motion</topic><topic>Neurotransmitters</topic><topic>Quality Control</topic><topic>Reproducibility of Results</topic><topic>Sensitivity and Specificity</topic><topic>Static Electricity</topic><topic>Stress, Mechanical</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Allen, Toby W.</creatorcontrib><creatorcontrib>Baştuğ, Turgut</creatorcontrib><creatorcontrib>Kuyucak, Serdar</creatorcontrib><creatorcontrib>Chung, Shin-Ho</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biophysical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Allen, Toby W.</au><au>Baştuğ, Turgut</au><au>Kuyucak, Serdar</au><au>Chung, Shin-Ho</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gramicidin A Channel as a Test Ground for Molecular Dynamics Force Fields</atitle><jtitle>Biophysical journal</jtitle><addtitle>Biophys J</addtitle><date>2003-04-01</date><risdate>2003</risdate><volume>84</volume><issue>4</issue><spage>2159</spage><epage>2168</epage><pages>2159-2168</pages><issn>0006-3495</issn><eissn>1542-0086</eissn><abstract>We use the well-known structural and functional properties of the gramicidin A channel to test the appropriateness of force fields commonly used in molecular dynamics (MD) simulations of ion channels. For this purpose, the high-resolution structure of the gramicidin A dimer is embedded in a dimyristoylphosphatidylcholine bilayer, and the potential of mean force of a K
+ ion is calculated along the channel axis using the umbrella sampling method. Calculations are performed using two of the most common force fields in MD simulations: CHARMM and GROMACS. Both force fields lead to large central barriers for K
+ ion permeation, that are substantially higher than those deduced from the physiological data by inverse methods. In long MD simulations lasting over 60
ns, several ions are observed to enter the binding site but none of them crossed the channel despite the presence of a large driving field. The present results, taken together with many earlier studies, highlights the shortcomings of the standard force fields used in MD simulations of ion channels and calls for construction of more appropriate force fields for this purpose.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>12668425</pmid><doi>10.1016/S0006-3495(03)75022-X</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Binding Sites Biophysical Theory and Modeling Cell Membrane Permeability Computer Simulation Crystallography - methods Dimerization Dimyristoylphosphatidylcholine - chemistry Gramicidin - chemistry Ion Channel Gating Ion Channels - chemistry Ions Lipid Bilayers - chemistry Macromolecular Substances Models, Molecular Molecular Conformation Molecules Motion Neurotransmitters Quality Control Reproducibility of Results Sensitivity and Specificity Static Electricity Stress, Mechanical |
| title | Gramicidin A Channel as a Test Ground for Molecular Dynamics Force Fields |
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