Molecular dynamics simulations of the unfolding of 2-microglobulin and its variants

In this study, we examined the unfolding processes of native [beta]

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Veröffentlicht in:	Protein engineering, design and selection design and selection, 2003-08, Vol.16 (8), p.561-575
Hauptverfasser:	Ma, B., Nussinov, R.
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container_title	Protein engineering, design and selection
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creator	Ma, B. Nussinov, R.
description	In this study, we examined the unfolding processes of native [beta]
doi_str_mv	10.1093/protein/gzg079
format	Article
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Three simulation models were used, molecular dynamics (MD) simulations with explicit water solvation, MD simulations with the CHARMM EEF1 force field and Langevin dynamics with the CHARMM EEF1 force field. Our simulations reproduce many of the experimentally observed structural changes. The most striking agreement is in the [beta]-strands to [alpha]-helix transition. In our simulations, strands [beta]<3<, [beta]<4< and [beta]<5< consistently change to [alpha]-helix, whereas [beta]<8< changes to an [alpha]-helix only briefly. Through comparisons of the conformational behavior of the native, the [Delta]N6 and the Lys-cut [beta]<2<-m, using the three simulation methods, we identified the consensus conformational changes that differentiate between the native [beta]<2<-m and its two variants. We found that the main effect of the removal of the N-terminal hexapeptide is to increase the separation between strands [beta]<2< and [beta]<6< and to facilitate the [beta] to [alpha] transition. On the other hand, the lysine cleavage only increases the flexibility of strand [beta]<5< and does not affect the interactions between strands [beta]<2< and [beta]<6<. These conformational changes may relate to polymerization tendencies of these variants.]]></description><identifier>ISSN: 1741-0126</identifier><identifier>EISSN: 1741-0134</identifier><identifier>DOI: 10.1093/protein/gzg079</identifier><language>eng</language><publisher>Oxford: Oxford Publishing Limited (England)</publisher><ispartof>Protein engineering, design and selection, 2003-08, Vol.16 (8), p.561-575</ispartof><rights>Copyright Oxford University Press(England) Aug 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1519-5d040432f7aadb6fc46f2aa0f36efb9953f5ba90beb674cddb27cf7980249cee3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Ma, B.</creatorcontrib><creatorcontrib>Nussinov, R.</creatorcontrib><title>Molecular dynamics simulations of the unfolding of 2-microglobulin and its variants</title><title>Protein engineering, design and selection</title><description><![CDATA[In this study, we examined the unfolding processes of native [beta]<2<-microglobulin and two related variants, one with an N-terminal hexapeptide deletion [Delta]N6 and another with Lys57-Asp58 cleavage, by high-temperature molecular dynamics simulations. Three simulation models were used, molecular dynamics (MD) simulations with explicit water solvation, MD simulations with the CHARMM EEF1 force field and Langevin dynamics with the CHARMM EEF1 force field. Our simulations reproduce many of the experimentally observed structural changes. The most striking agreement is in the [beta]-strands to [alpha]-helix transition. In our simulations, strands [beta]<3<, [beta]<4< and [beta]<5< consistently change to [alpha]-helix, whereas [beta]<8< changes to an [alpha]-helix only briefly. Through comparisons of the conformational behavior of the native, the [Delta]N6 and the Lys-cut [beta]<2<-m, using the three simulation methods, we identified the consensus conformational changes that differentiate between the native [beta]<2<-m and its two variants. We found that the main effect of the removal of the N-terminal hexapeptide is to increase the separation between strands [beta]<2< and [beta]<6< and to facilitate the [beta] to [alpha] transition. On the other hand, the lysine cleavage only increases the flexibility of strand [beta]<5< and does not affect the interactions between strands [beta]<2< and [beta]<6<. These conformational changes may relate to polymerization tendencies of these variants.]]></description><issn>1741-0126</issn><issn>1741-0134</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNo9kM1KAzEUhYMoWKtb18H9tPmbiVlKUStU3Nh1yO-YMk1qMiPUp_FZfDKntLi6l8Ph3Hs-AG4xmmEk6HyXU-9CnLffLeLiDEwwZ7hCmLLz_500l-CqlA1CpOEYT8D6NXXODJ3K0O6j2gZTYAnbUehDigUmD_sPB4foU2dDbA_C7w-pRmNObZf00IUIVbQw9AV-qRxU7Ms1uPCqK-7mNKdg_fT4vlhWq7fnl8XDqjK4xqKqLWKIUeK5UlY33rDGE6WQp43zWoia-lorgbTTDWfGWk248VzcI8KEcY5Owd0xd-z-ObjSy00achxPSkLqGhE-xk_B7GgaPy4lOy93OWxV3kuM5IGcPJGTR3L0D_TyZqM</recordid><startdate>20030801</startdate><enddate>20030801</enddate><creator>Ma, B.</creator><creator>Nussinov, R.</creator><general>Oxford Publishing Limited (England)</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>P64</scope></search><sort><creationdate>20030801</creationdate><title>Molecular dynamics simulations of the unfolding of 2-microglobulin and its variants</title><author>Ma, B. ; Nussinov, R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1519-5d040432f7aadb6fc46f2aa0f36efb9953f5ba90beb674cddb27cf7980249cee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ma, B.</creatorcontrib><creatorcontrib>Nussinov, R.</creatorcontrib><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</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>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Protein engineering, design and selection</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ma, B.</au><au>Nussinov, R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular dynamics simulations of the unfolding of 2-microglobulin and its variants</atitle><jtitle>Protein engineering, design and selection</jtitle><date>2003-08-01</date><risdate>2003</risdate><volume>16</volume><issue>8</issue><spage>561</spage><epage>575</epage><pages>561-575</pages><issn>1741-0126</issn><eissn>1741-0134</eissn><abstract><![CDATA[In this study, we examined the unfolding processes of native [beta]<2<-microglobulin and two related variants, one with an N-terminal hexapeptide deletion [Delta]N6 and another with Lys57-Asp58 cleavage, by high-temperature molecular dynamics simulations. Three simulation models were used, molecular dynamics (MD) simulations with explicit water solvation, MD simulations with the CHARMM EEF1 force field and Langevin dynamics with the CHARMM EEF1 force field. Our simulations reproduce many of the experimentally observed structural changes. The most striking agreement is in the [beta]-strands to [alpha]-helix transition. In our simulations, strands [beta]<3<, [beta]<4< and [beta]<5< consistently change to [alpha]-helix, whereas [beta]<8< changes to an [alpha]-helix only briefly. Through comparisons of the conformational behavior of the native, the [Delta]N6 and the Lys-cut [beta]<2<-m, using the three simulation methods, we identified the consensus conformational changes that differentiate between the native [beta]<2<-m and its two variants. We found that the main effect of the removal of the N-terminal hexapeptide is to increase the separation between strands [beta]<2< and [beta]<6< and to facilitate the [beta] to [alpha] transition. On the other hand, the lysine cleavage only increases the flexibility of strand [beta]<5< and does not affect the interactions between strands [beta]<2< and [beta]<6<. These conformational changes may relate to polymerization tendencies of these variants.]]></abstract><cop>Oxford</cop><pub>Oxford Publishing Limited (England)</pub><doi>10.1093/protein/gzg079</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record>
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title	Molecular dynamics simulations of the unfolding of 2-microglobulin and its variants
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