Role of non-covalent interactions for determining the folding rate of two-state proteins.

Understanding the factors influencing the folding rate of proteins is a challenging problem. In this work, we have analyzed the role of non-covalent interactions for the folding rate of two-state proteins by free-energy approach. We have computed the free-energy terms, hydrophobic, electrostatic, hydrogen-bonding and van der Waals free energies. The hydrophobic free energy has been divided into the contributions from different atoms, carbon, neutral nitrogen and oxygen, charged nitrogen and oxygen, and sulfur. All the free-energy terms have been related with the folding rates of 28 two-state proteins with single and multiple correlation coefficients. We found that the hydrophobic free energy due to carbon atoms and hydrogen-bonding free energy play important roles to determine the folding rate in combination with other free energies. The normalized energies with total number of residues showed better results than the total energy of the protein. The comparison of amino acid properties with free-energy terms indicates that the energetic terms explain better the folding rate than amino acid properties. Further, the combination of free energies with topological parameters yielded the correlation of 0.91. The present study demonstrates the importance of topology for determining the folding rate of two-state proteins.

[1]  D. Baker,et al.  Contact order, transition state placement and the refolding rates of single domain proteins. , 1998, Journal of molecular biology.

[2]  Kevin W Plaxco,et al.  The topomer search model: A simple, quantitative theory of two‐state protein folding kinetics , 2003, Protein science : a publication of the Protein Society.

[3]  P Argos,et al.  Protein thermal stability, hydrogen bonds, and ion pairs. , 1997, Journal of molecular biology.

[4]  J. Thornton,et al.  Satisfying hydrogen bonding potential in proteins. , 1994, Journal of molecular biology.

[5]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..

[6]  J. D. Morgan,et al.  Molecular dynamics of ferrocytochrome c. Magnitude and anisotropy of atomic displacements. , 1981, Journal of molecular biology.

[7]  B. Matthews,et al.  Enhanced protein thermostability from designed mutations that interact with α-helix dipoles , 1990, Nature.

[8]  M. Gromiha,et al.  Comparison between long-range interactions and contact order in determining the folding rate of two-state proteins: application of long-range order to folding rate prediction. , 2001, Journal of molecular biology.

[9]  Aaron R. Dinner,et al.  The roles of stability and contact order in determining protein folding rates , 2001, Nature Structural Biology.

[10]  P. Kollman,et al.  A Second Generation Force Field for the Simulation of Proteins, Nucleic Acids, and Organic Molecules , 1995 .

[11]  M. Gromiha,et al.  Important amino acid properties for enhanced thermostability from mesophilic to thermophilic proteins. , 1999, Biophysical chemistry.

[12]  M. Michael Gromiha,et al.  Importance of Native-State Topology for Determining the Folding Rate of Two-State Proteins , 2003, J. Chem. Inf. Comput. Sci..

[13]  J. Thornton.  Disulphide bridges in globular proteins. , 1981, Journal of molecular biology.

[14]  M. Gromiha,et al.  Role of structural and sequence information in the prediction of protein stability changes: comparison between buried and partially buried mutations. , 1999, Protein engineering.

[15]  M. Michael Gromiha,et al.  On the conformational stability of folded proteins , 1994 .

[16]  Hongyi Zhou,et al.  Folding rate prediction using total contact distance. , 2002, Biophysical journal.

[17]  A. D. McLachlan,et al.  Solvation energy in protein folding and binding , 1986, Nature.

[18]  M Michael Gromiha,et al.  Importance of mutant position in Ramachandran plot for predicting protein stability of surface mutations. , 2002, Biopolymers.

[19]  D Baker,et al.  Topology, stability, sequence, and length: defining the determinants of two-state protein folding kinetics. , 2000, Biochemistry.

[20]  A. Fersht,et al.  Conformational equilibria in -and -chymotrypsin. The energetics and importance of the salt bridge. , 1972, Journal of molecular biology.

[21]  R. Nussinov,et al.  Factors enhancing protein thermostability. , 2000, Protein engineering.

[22]  K Wüthrich,et al.  The influence of a single salt bridge on static and dynamic features of the globular solution conformation of the basic pancreatic trypsin inhibitor. 1H and 13C nuclear-magnetic-resonance studies of the native and the transaminated inhibitor. , 1978, European journal of biochemistry.

[23]  S. Marqusee,et al.  Experimental evaluation of topological parameters determining protein-folding rates , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[24]  M Bycroft,et al.  Stabilization of protein structure by interaction of alpha-helix dipole with a charged side chain. , 1988, Nature.

[25]  B. Matthews,et al.  Enhanced protein thermostability from designed mutations that interact with alpha-helix dipoles. , 1988, Nature.

[26]  M. Gromiha,et al.  Relationship Between Amino Acid Properties and Protein Stability: Buried Mutations , 1999, Journal of protein chemistry.

[27]  Kevin W Plaxco,et al.  Comparison of the folding processes of distantly related proteins. Importance of hydrophobic content in folding. , 2003, Journal of molecular biology.

[28]  Linxi Zhang,et al.  Folding rate prediction based on neural network model , 2003 .

[29]  M. Gromiha,et al.  Importance of Surrounding Residues for Protein Stability of Partially Buried Mutations , 2000, Journal of biomolecular structure & dynamics.

[30]  M. Perutz,et al.  Stereochemical basis of heat stability in bacterial ferredoxins and in haemoglobin A2 , 1975, Nature.

[31]  Haipeng Gong,et al.  Local secondary structure content predicts folding rates for simple, two-state proteins. , 2003, Journal of molecular biology.

[32]  W. Goddard,et al.  First principles prediction of protein folding rates. , 1999, Journal of molecular biology.

[33]  V. Muñoz,et al.  A simple model for calculating the kinetics of protein folding from three-dimensional structures. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[34]  B Honig,et al.  Electrostatic contributions to the stability of hyperthermophilic proteins. , 1999, Journal of molecular biology.

[35]  Dmitry N Ivankov,et al.  Chain length is the main determinant of the folding rate for proteins with three‐state folding kinetics , 2003, Proteins.

[36]  Akinori Sarai,et al.  ProTherm, Thermodynamic Database for Proteins and Mutants: developments in version 3.0 , 2002, Nucleic Acids Res..

[37]  Alan R. Fersht,et al.  Stabilization of protein structure by interaction of α-helix dipole with a charged side chain , 1988, Nature.

[38]  V. Pande,et al.  Cooperativity, smooth energy landscapes and the origins of topology-dependent protein folding rates. , 2003, Journal of Molecular Biology.