Molecular Dynamics Simulation and Binding Energy Calculation for Estimation of Oligonucleotide Duplex Thermostability in RNA-Based Therapeutics
For oligonucleotide-based therapeutics, a thorough understanding of the thermodynamic properties of duplex formation is critical to developing stable and potent drugs. For unmodified small interfering RNA (siRNA), DNA antisense oligonucleotide (AON) and locked nucleic acid (LNA), DNA/LNA modified ol...
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| Veröffentlicht in: | Journal of chemical information and modeling 2011-08, Vol.51 (8), p.1957-1965 |
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| container_end_page | 1965 |
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| container_issue | 8 |
| container_start_page | 1957 |
| container_title | Journal of chemical information and modeling |
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| creator | Shen, Lingling Johnson, Theresa L Clugston, Susan Huang, Hongwei Butenhof, Kenneth J Stanton, Robert V |
| description | For oligonucleotide-based therapeutics, a thorough understanding of the thermodynamic properties of duplex formation is critical to developing stable and potent drugs. For unmodified small interfering RNA (siRNA), DNA antisense oligonucleotide (AON) and locked nucleic acid (LNA), DNA/LNA modified oligonucleotides, nearest neighbor (NN) methods can be effectively used to quickly and accurately predict duplex thermodynamic properties such as melting point. Unfortunately, for chemically modified olignonucleotides, there has been no accurate prediction method available. Here we describe the potential of estimating melting temperature (T m) for nonstandard oligonucleotides by using the correlation of the experimental T m with the calculated duplex binding energy (BE) for oligonucleotides of a given length. This method has been automated into a standardized molecular dynamics (MD) protocol through Pipeline Pilot (PP) using the CHARMm component in Discovery Studio (DS). Results will be presented showing the correlation of the predicted data with experiment for both standard and chemically modified siRNA and AON. |
| doi_str_mv | 10.1021/ci200141j |
| format | Article |
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For unmodified small interfering RNA (siRNA), DNA antisense oligonucleotide (AON) and locked nucleic acid (LNA), DNA/LNA modified oligonucleotides, nearest neighbor (NN) methods can be effectively used to quickly and accurately predict duplex thermodynamic properties such as melting point. Unfortunately, for chemically modified olignonucleotides, there has been no accurate prediction method available. Here we describe the potential of estimating melting temperature (T m) for nonstandard oligonucleotides by using the correlation of the experimental T m with the calculated duplex binding energy (BE) for oligonucleotides of a given length. This method has been automated into a standardized molecular dynamics (MD) protocol through Pipeline Pilot (PP) using the CHARMm component in Discovery Studio (DS). Results will be presented showing the correlation of the predicted data with experiment for both standard and chemically modified siRNA and AON.</description><identifier>ISSN: 1549-9596</identifier><identifier>EISSN: 1549-960X</identifier><identifier>DOI: 10.1021/ci200141j</identifier><identifier>PMID: 21702481</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Automation, Laboratory ; Binding sites ; Biological and medical sciences ; Chemistry, Pharmaceutical - methods ; Computer simulation ; Deoxyribonucleic acid ; DNA ; DNA - analysis ; DNA - chemistry ; DNA - metabolism ; Drug Stability ; General pharmacology ; Genetic Therapy - methods ; Humans ; Medical sciences ; Molecular Dynamics Simulation ; Molecular structure ; Molecular Targeted Therapy - methods ; Nucleic Acid Conformation ; Nucleic Acid Heteroduplexes - chemistry ; Nucleic Acid Heteroduplexes - genetics ; Oligonucleotides - analysis ; Oligonucleotides - chemistry ; Oligonucleotides - metabolism ; Oligonucleotides, Antisense - analysis ; Oligonucleotides, Antisense - chemistry ; Oligonucleotides, Antisense - metabolism ; Pharmaceutical Modeling ; Pharmaceutical Preparations - analysis ; Pharmaceutical Preparations - chemistry ; Pharmaceutical technology. 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Chem. Inf. Model</addtitle><description>For oligonucleotide-based therapeutics, a thorough understanding of the thermodynamic properties of duplex formation is critical to developing stable and potent drugs. For unmodified small interfering RNA (siRNA), DNA antisense oligonucleotide (AON) and locked nucleic acid (LNA), DNA/LNA modified oligonucleotides, nearest neighbor (NN) methods can be effectively used to quickly and accurately predict duplex thermodynamic properties such as melting point. Unfortunately, for chemically modified olignonucleotides, there has been no accurate prediction method available. Here we describe the potential of estimating melting temperature (T m) for nonstandard oligonucleotides by using the correlation of the experimental T m with the calculated duplex binding energy (BE) for oligonucleotides of a given length. This method has been automated into a standardized molecular dynamics (MD) protocol through Pipeline Pilot (PP) using the CHARMm component in Discovery Studio (DS). 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Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Small Interfering - analysis</subject><subject>RNA, Small Interfering - chemistry</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Spectrophotometry</subject><subject>Thermodynamics</subject><subject>Transition Temperature</subject><issn>1549-9596</issn><issn>1549-960X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpl0VFrFDEQAOAgiq3XPvgHJAgiPqxNstls9rG9nlWoLbQVfFuy2cmZI5ucyS54v8K_bOzd9UCfksx8zAwZhF5T8pESRs-0ZYRQTlfP0DGteFM0gnx_vr9XjThCr1JaEVKWjWAv0RGjNWFc0mP0-2twoCenIr7ceDVYnfC9HXJgtMFj5Xt8YX1v_RIvPMTlBs-V0_u0CREv0miH7TMYfOvsMvhJOwij7QFfTmsHv_DDD4hDSKPqrLPjBluP727OiwuVoH9MqjVMY25-gl4Y5RKc7s4Z-vZp8TD_XFzfXn2Zn18Xipf1WBgKXd2XxPBOANG6rsoeOl2LnnBiGDem6yrWKFnKDDgjRhvBOsUkZ5oxXc7Q-23ddQw_J0hjO9ikwTnlIUyplZJL3jBZZ_n2H7kKU_R5uIxk2VCam8_Qhy3SMaQUwbTrmH8lblpK2r87ap92lO2bXcGpG6B_kvulZPBuB1TSypmovLbp4DgXlRD84JROh6H-b_gHW5KnlQ</recordid><startdate>20110822</startdate><enddate>20110822</enddate><creator>Shen, Lingling</creator><creator>Johnson, Theresa L</creator><creator>Clugston, Susan</creator><creator>Huang, Hongwei</creator><creator>Butenhof, Kenneth J</creator><creator>Stanton, Robert V</creator><general>American Chemical Society</general><scope>IQODW</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>7SC</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>JQ2</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>7X8</scope></search><sort><creationdate>20110822</creationdate><title>Molecular Dynamics Simulation and Binding Energy Calculation for Estimation of Oligonucleotide Duplex Thermostability in RNA-Based Therapeutics</title><author>Shen, Lingling ; Johnson, Theresa L ; Clugston, Susan ; Huang, Hongwei ; Butenhof, Kenneth J ; Stanton, Robert V</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a437t-f1eb7d30f4b6e0cc753debc76d040f24ffbb529a838b6e420fcf62ba2842c22c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Automation, Laboratory</topic><topic>Binding sites</topic><topic>Biological and medical sciences</topic><topic>Chemistry, Pharmaceutical - methods</topic><topic>Computer simulation</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA - analysis</topic><topic>DNA - chemistry</topic><topic>DNA - metabolism</topic><topic>Drug Stability</topic><topic>General pharmacology</topic><topic>Genetic Therapy - methods</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Molecular Dynamics Simulation</topic><topic>Molecular structure</topic><topic>Molecular Targeted Therapy - methods</topic><topic>Nucleic Acid Conformation</topic><topic>Nucleic Acid Heteroduplexes - chemistry</topic><topic>Nucleic Acid Heteroduplexes - genetics</topic><topic>Oligonucleotides - analysis</topic><topic>Oligonucleotides - chemistry</topic><topic>Oligonucleotides - metabolism</topic><topic>Oligonucleotides, Antisense - analysis</topic><topic>Oligonucleotides, Antisense - chemistry</topic><topic>Oligonucleotides, Antisense - metabolism</topic><topic>Pharmaceutical Modeling</topic><topic>Pharmaceutical Preparations - analysis</topic><topic>Pharmaceutical Preparations - chemistry</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Small Interfering - analysis</topic><topic>RNA, Small Interfering - chemistry</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Spectrophotometry</topic><topic>Thermodynamics</topic><topic>Transition Temperature</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shen, Lingling</creatorcontrib><creatorcontrib>Johnson, Theresa L</creatorcontrib><creatorcontrib>Clugston, Susan</creatorcontrib><creatorcontrib>Huang, Hongwei</creatorcontrib><creatorcontrib>Butenhof, Kenneth J</creatorcontrib><creatorcontrib>Stanton, Robert V</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Computer and Information Systems Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of chemical information and modeling</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shen, Lingling</au><au>Johnson, Theresa L</au><au>Clugston, Susan</au><au>Huang, Hongwei</au><au>Butenhof, Kenneth J</au><au>Stanton, Robert V</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular Dynamics Simulation and Binding Energy Calculation for Estimation of Oligonucleotide Duplex Thermostability in RNA-Based Therapeutics</atitle><jtitle>Journal of chemical information and modeling</jtitle><addtitle>J. Chem. Inf. Model</addtitle><date>2011-08-22</date><risdate>2011</risdate><volume>51</volume><issue>8</issue><spage>1957</spage><epage>1965</epage><pages>1957-1965</pages><issn>1549-9596</issn><eissn>1549-960X</eissn><abstract>For oligonucleotide-based therapeutics, a thorough understanding of the thermodynamic properties of duplex formation is critical to developing stable and potent drugs. For unmodified small interfering RNA (siRNA), DNA antisense oligonucleotide (AON) and locked nucleic acid (LNA), DNA/LNA modified oligonucleotides, nearest neighbor (NN) methods can be effectively used to quickly and accurately predict duplex thermodynamic properties such as melting point. Unfortunately, for chemically modified olignonucleotides, there has been no accurate prediction method available. Here we describe the potential of estimating melting temperature (T m) for nonstandard oligonucleotides by using the correlation of the experimental T m with the calculated duplex binding energy (BE) for oligonucleotides of a given length. This method has been automated into a standardized molecular dynamics (MD) protocol through Pipeline Pilot (PP) using the CHARMm component in Discovery Studio (DS). Results will be presented showing the correlation of the predicted data with experiment for both standard and chemically modified siRNA and AON.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>21702481</pmid><doi>10.1021/ci200141j</doi><tpages>9</tpages></addata></record> |
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| ispartof | Journal of chemical information and modeling, 2011-08, Vol.51 (8), p.1957-1965 |
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| subjects | Automation, Laboratory Binding sites Biological and medical sciences Chemistry, Pharmaceutical - methods Computer simulation Deoxyribonucleic acid DNA DNA - analysis DNA - chemistry DNA - metabolism Drug Stability General pharmacology Genetic Therapy - methods Humans Medical sciences Molecular Dynamics Simulation Molecular structure Molecular Targeted Therapy - methods Nucleic Acid Conformation Nucleic Acid Heteroduplexes - chemistry Nucleic Acid Heteroduplexes - genetics Oligonucleotides - analysis Oligonucleotides - chemistry Oligonucleotides - metabolism Oligonucleotides, Antisense - analysis Oligonucleotides, Antisense - chemistry Oligonucleotides, Antisense - metabolism Pharmaceutical Modeling Pharmaceutical Preparations - analysis Pharmaceutical Preparations - chemistry Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Ribonucleic acid RNA RNA, Small Interfering - analysis RNA, Small Interfering - chemistry RNA, Small Interfering - metabolism Spectrophotometry Thermodynamics Transition Temperature |
| title | Molecular Dynamics Simulation and Binding Energy Calculation for Estimation of Oligonucleotide Duplex Thermostability in RNA-Based Therapeutics |
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