|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
15
|
|
pubmed:dateCreated |
1998-8-20
|
|
pubmed:abstractText |
Experimental data from protein engineering studies and NMR spectroscopy have been used by theoreticians to develop algorithms for helix propensity and to benchmark computer simulations of folding pathways and energy landscapes. Molecular dynamic simulations of the unfolding of chymotrypsin inhibitor 2 (CI2) have provided detailed structural models of the transition state ensemble for unfolding/folding of the protein. We now have used the simulated transition state structures to design faster folding mutants of CI2. The models pinpoint a number of unfavorable local interactions at the carboxyl terminus of the single alpha-helix and in the protease-binding loop region of CI2. By removing these interactions or replacing them with stabilizing ones, we have increased the rate of folding of the protein up to 40-fold (tau = 0.4 ms). This correspondence, and other examples of agreement between experiment and theory in general, Phi-values and molecular dynamics simulations, in particular, suggest that significant progress has been made toward describing complete folding pathways at atomic resolution by combining experiment and simulation.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-11607448,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-1404368,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-15299354,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-1557131,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-1784198,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-1931967,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-2739734,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-2812029,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-2845278,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-2845279,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-4358627,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-7490748,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-7490749,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-7552710,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-7563082,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-7568125,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-7577956,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-7604023,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-7664054,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-7773748,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-7844817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-7937967,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-7937968,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-7937969,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-8060971,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-8117669,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-8127876,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-8193956,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-8538750,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-8609633,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-8609634,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-8696969,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-8836105,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-8897601,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-9023333,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-9079363,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-9079374,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-9079379,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-9079381,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-9095199,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-9149151,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-9200680,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-9391038,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9671702-9395391
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jul
|
|
pubmed:issn |
0027-8424
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
21
|
|
pubmed:volume |
95
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
8473-8
|
|
pubmed:dateRevised |
2009-11-18
|
|
pubmed:meshHeading |
|
|
pubmed:year |
1998
|
|
pubmed:articleTitle |
Synergy between simulation and experiment in describing the energy landscape of protein folding.
|
|
pubmed:affiliation |
Cambridge University Chemical Laboratory and Cambridge Centre for Protein Engineering, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, United Kingdom.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
