A self-consistent knowledge-based approach to protein design.
A simple and very efficient protein design strategy is proposed by developing some recently introduced theoretical tools which have been successfully applied to exactly solvable protein models. The design approach is implemented by using three amino acid classes and it is based on the minimization of an appropriate energy function. For a given native state the results of the design procedure are compared, through a statistical analysis, with the properties of an ensemble of sequences folding in the same conformation. If the success rate is computed on those sites designed with high confidence, it can be as high as 80%. The method is also able to identify key sites for the folding process: results for 2ci2 and barnase are in very good agreement with experimental results.
Rossi
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A
International School for Advanced Studies and INFM, I-34014 Trieste, Italy. rossi@sissa.it
Micheletti
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C
Seno
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F
Maritan
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A
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000145:classification; D001185:Artificial Intelligence; D001426:Bacterial Proteins; D055592:Biophysical Phenomena; D001703:Biophysics; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D017124:Conserved Sequence; D016208:Databases, Factual; D015195:Drug Design; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D012260:Ribonucleases / Q000737:chemistry; D015842:Serine Proteinase Inhibitors / Q000737:chemistry; D013816:Thermodynamics
D000596:Amino Acids; D001426:Bacterial Proteins; D011506:Proteins; D015842:Serine Proteinase Inhibitors; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease; D002918:Chymotrypsin