Calculation of protein conformation by global optimization of a potential energy function

A novel hierarchical approach to protein folding has been applied to compute the unknown structures of seven target proteins provided by CASP3. The approach is based exclusively on the global optimization of a potential energy function for a united‐residue model by conformational space annealing, followed by energy refinement using an all‐atom potential. Comparison of the submitted models for five globular proteins with the experimental structures shows that the conformations of large fragments (∼60 aa) were predicted with rmsds of 4.2–6.8 Å for the Cα atoms. Our lowest‐energy models for targets T0056 and T0061 were particularly successful, producing the correct fold of approximately 52% and 80% of the structures, respectively. These results support the thermodynamic hypothesis that protein structure can be computed solely by global optimization of a potential energy function for a given amino acid sequence. Proteins Suppl 1999;3:204–208. © 1999 Wiley‐Liss, Inc.

[1]  C. Anfinsen.  Principles that govern the folding of protein chains. , 1973, Science.

[2]  H. Scheraga,et al.  Empirical solvation models can be used to differentiate native from near‐native conformations of bovine pancreatic trypsin inhibitor , 1991, Proteins.

[3]  S. Rackovsky,et al.  Prediction of protein conformation on the basis of a search for compact structures: Test on avian pancreatic polypeptide , 1993, Protein science : a publication of the Protein Society.

[4]  S. Rackovsky,et al.  Calculation of protein backbone geometry from α‐carbon coordinates based on peptide‐group dipole alignment , 1993, Protein science : a publication of the Protein Society.

[5]  H. Scheraga,et al.  Energy parameters in polypeptides. 10. Improved geometrical parameters and nonbonded interactions for use in the ECEPP/3 algorithm, with application to proline-containing peptides , 1994 .

[6]  H A Scheraga,et al.  Recent developments in the theory of protein folding: searching for the global energy minimum. , 1996, Biophysical chemistry.

[7]  A. Liwo,et al.  A united‐residue force field for off‐lattice protein‐structure simulations. II. Parameterization of short‐range interactions and determination of weights of energy terms by Z‐score optimization , 1997 .

[8]  Adam Liwo,et al.  A united-residue force field for off-lattice protein-structure simulations. II. Parameterization of short-range interactions and determination of weights of energy terms by Z-score optimization , 1997, J. Comput. Chem..

[9]  Jooyoung Lee,et al.  New optimization method for conformational energy calculations on polypeptides: Conformational space annealing , 1997, J. Comput. Chem..

[10]  Adam Liwo,et al.  A united-residue force field for off-lattice protein-structure simulations. I. Functional forms and parameters of long-range side-chain interaction potentials from protein crystal data , 1997, J. Comput. Chem..

[11]  L. Mirny,et al.  Protein structure prediction by threading. Why it works and why it does not. , 1998, Journal of molecular biology.

[12]  H A Scheraga,et al.  New developments of the electrostatically driven Monte Carlo method: test on the membrane-bound portion of melittin. , 1998, Biopolymers.

[13]  Fan Yang,et al.  Crystal structure of Escherichia coli HdeA , 1998, Nature Structural Biology.

[14]  A. Liwo,et al.  United‐residue force field for off‐lattice protein‐structure simulations: III. Origin of backbone hydrogen‐bonding cooperativity in united‐residue potentials , 1998 .

[15]  S. Rackovsky,et al.  Conformational analysis of the 20-residue membrane-bound portion of melittin by conformational space annealing. , 1998, Biopolymers.

[16]  C. Orengo,et al.  Analysis and assessment of ab initio three‐dimensional prediction, secondary structure, and contacts prediction , 1999, Proteins.

[17]  Harold A. Scheraga,et al.  Conformational space annealing by parallel computations: Extensive conformational search of Met‐enkephalin and of the 20‐residue membrane‐bound portion of melittin , 1999 .

[18]  A. Liwo,et al.  Energy-based de novo protein folding by conformational space annealing and an off-lattice united-residue force field: application to the 10-55 fragment of staphylococcal protein A and to apo calbindin D9K. , 1999, Proceedings of the National Academy of Sciences of the United States of America.