|4pti, resolution 1.50Å ()|
THE GEOMETRY OF THE REACTIVE SITE AND OF THE PEPTIDE GROUPS IN TRYPSIN, TRYPSINOGEN AND ITS COMPLEXES WITH INHIBITORS
We have explored the application of genetic algorithms (GA) to the determination of protein structure from sequence, using a full atom representation. A free energy function with point charge electrostatics and an area based solvation model is used. The method is found to be superior to previously investigated Monte Carlo algorithms. For selected fragments, up to 14 residues long, the lowest free energy structures produced by the GA are similar in conformation to the corresponding experimental structures in most cases. There are three main conclusions from these results. First, the genetic algorithm is an effective method for searching amongst the compact conformations of a polypeptide chain. Second, the free energy function is generally able to select native-like conformations. However, some deficiencies are identified, and further development is proposed. Third, the selection of native-like conformations for some protein fragments establishes that in these cases the conformation observed in the full protein structure is largely context independent. The implications for the nature of protein folding pathways are discussed.
Protein folding simulations with genetic algorithms and a detailed molecular description., Pedersen JT, Moult J, J Mol Biol. 1997 Jun 6;269(2):240-59. PMID:009191068
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
4pti is a 1 chain structure with sequence from Bos taurus. This structure supersedes the now removed PDB entries and 2pti. The October 2011 RCSB PDB Molecule of the Month feature on PDB Pioneers by David Goodsell is 10.2210/rcsb_pdb/mom_2011_10. Full crystallographic information is available from OCA.
- Pedersen JT, Moult J. Protein folding simulations with genetic algorithms and a detailed molecular description. J Mol Biol. 1997 Jun 6;269(2):240-59. PMID:9191068 doi:10.1006/jmbi.1997.1010
- Hansen PE, Zhang W, Lauritzen C, Bjorn S, Petersen LC, Norris K, Olsen OH, Betzel C. 13C NMR, X-ray, and differential scanning calorimetry investigations of truncated BPTI (aprotinin) analogues. Biochemistry. 1998 Mar 17;37(11):3645-53. PMID:9521683 doi:10.1021/bi972282u