title: Addition of side chains to a known backbone with defined side-chain centroids.
abstract: An automatic procedure is proposed for adding side chains to a protein backbone; it is based on optimization of a simplified energy function for peptide side chains, given its backbone and positions of side-chain centroids. The energy is expressed as a sum of the energies of interaction between side chains, and a harmonic penalty function accounting for the preservation of the positions of the C(alpha) atoms and the side-chain centroids. The energy of side-chain interactions is calculated with the soft-sphere ECEPP/3 potential. A Monte Carlo search is carried out to explore all possible side-chain orientations within a fixed backbone and side-chain centroid positions. The initial, usually extended, side-chain conformations are taken directly from the ECEPP/3 database. The procedure was tested on six experimental (X-ray or NMR) structures: immunoglobulin binding protein (PDB code 1IGD, an alpha+beta-protein); transcription factor PML (PDB code 1BOR, a 49-104 fragment of the ring finger domain, predominantly beta-protein); bovine pancreatic trypsin inhibitor (crystal form II) (PDB code 1BPI, an alpha+beta-protein); the monomer of human deoxyhemoglobin (PDB code 1BZ0, an alpha-helical structure); chain A of alcohol dehydrogenase from Drosophila lebanonensis (PDB code 1A4U); as well as on the 10-55 portion of the B domain of staphylococcal protein A (PDB code 1BDD). In all cases except 1BPI, the data for the algorithm (i.e. the backbone or C(alpha) coordinates and the positions of side-chain centroids) were taken from the experimental structures. For protein A, the C(alpha) coordinates and positions of side-chain centroids were also taken from the 1.9-A-resolution model predicted by the UNRES force field. In all comparisons with experimental structures, complete side-chain geometry was reconstructed with a root-mean-square (RMS) deviation of approximately 0.6-0.9 A from the heavy atoms when complete backbone and side-chain-centroid coordinates were used in reconstruction, or approximately 1.0 A when the C(alpha) and centroid coordinates were used.
authors.affiliation: Baker Laboratory of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853-1301, USA.
authors.forename: Rajmund
authors.initials: R
authors.lastname: Kaźmierkiewicz
authors.forename: Adam
authors.initials: A
authors.lastname: Liwo
authors.forename: Harold A
authors.initials: HA
authors.lastname: Scheraga
mesh_terms: D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D007611:Aprotinin / Q000737:chemistry; D002352:Carrier Proteins / Q000737:chemistry; D002417:Cattle; D019295:Computational Biology; D018360:Crystallography, X-Ray; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry; D009010:Monte Carlo Method; D009363:Neoplasm Proteins / Q000737:chemistry; D009687:Nuclear Proteins; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D000071156:Promyelocytic Leukemia Protein; D017433:Protein Structure, Secondary; D011506:Proteins / Q000138:chemical synthesis* / Q000737:chemistry*; D013205:Staphylococcal Protein A / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry; D025521:Tumor Suppressor Proteins
chemical_list: D000596:Amino Acids; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010455:Peptides; D000071156:Promyelocytic Leukemia Protein; D011506:Proteins; D013205:Staphylococcal Protein A; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D007611:Aprotinin