The interstrand amino acid pairs play a significant role in determining the parallel or antiparallel orientation of beta-strands.

It is widely considered that it is not appropriate to treat beta-pairs in isolation, since other secondary structural models (such as helices, coils), protein topology and protein tertiary structures would limit beta-strand pairing. However, to understand the underlying mechanisms of beta-sheet formation, studies ought to be performed separately on more concrete aspects. In this study, we focus on the parallel or antiparallel orientation of beta-strands. First, statistical analysis was performed on the relative frequencies of the interstrand amino acid pairs within parallel and antiparallel beta-strands. Consequently, features were extracted by singular value decomposition from the statistical results. By using the support vector machine to distinguish the features extracted from the two types of beta-strands, high accuracy was achieved (up to 99.4%). This suggests that the interstrand amino acid pairs play a significant role in determining the parallel or antiparallel orientation of beta-strands. These results may provide useful information for developing other useful algorithms to examine to the beta-strand folding pathways, and could eventually lead to protein structure predictions.

[1]  D. Osguthorpe.  Ab initio protein folding. , 2000, Current opinion in structural biology.

[2]  Qian Li,et al.  Prediction of the β-Hairpins in Proteins Using Support Vector Machine , 2008 .

[3]  Parviz Abdolmaleki,et al.  gamma-Turn types prediction in proteins using the support vector machines. , 2007, Journal of theoretical biology.

[4]  K. Chou,et al.  Prediction of beta-turns. , 1979, Journal of protein chemistry.

[5]  Robert S. McDowell,et al.  A Minimal Peptide Scaffold for β-Turn Display: Optimizing a Strand Position in Disulfide-Cyclized β-Hairpins , 2001 .

[6]  Janet M. Thornton,et al.  Toward predicting protein topology: An approach to identifying β hairpins , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[7]  V. Thorsson,et al.  HMMSTR: a hidden Markov model for local sequence-structure correlations in proteins. , 2000, Journal of molecular biology.

[8]  L. Gregoret,et al.  Context-dependence of Amino Acid Residue Pairing in Antiparallel β-She?ets , 1999 .

[9]  Kuo-Chen Chou,et al.  Support vector machines for the classification and prediction of β‐turn types , 2002, Journal of peptide science : an official publication of the European Peptide Society.

[10]  Pierre Baldi,et al.  ICBS: a database of interactions between protein chains mediated by ?-sheet formation , 2004, Bioinform..

[11]  J. Nowick.  Exploring beta-sheet structure and interactions with chemical model systems. , 2008, Accounts of chemical research.

[12]  David Baker,et al.  Protein Structure Prediction Using Rosetta , 2004, Numerical Computer Methods, Part D.

[13]  Tao Zhang,et al.  SHEETSPAIR: A Database of Amino Acid Pairs in Protein Sheet Structures , 2007, Data Sci. J..

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

[15]  P Rotkiewicz,et al.  Generalized comparative modeling (GENECOMP): A combination of sequence comparison, threading, and lattice modeling for protein structure prediction and refinement , 2001, Proteins.

[16]  Y. Mandel-Gutfreund,et al.  Contributions of residue pairing to beta-sheet formation: conservation and covariation of amino acid residue pairs on antiparallel beta-strands. , 2001, Journal of molecular biology.

[17]  M. Searle,et al.  Design of beta-sheet systems for understanding the thermodynamics and kinetics of protein folding. , 2004, Current opinion in structural biology.

[18]  Julian Lee,et al.  Protein structure prediction based on fragment assembly and parameter optimization. , 2005, Biophysical chemistry.

[19]  Acr Martin,et al.  Amino Acid Pairing Preferences in Parallel β-Sheets in Proteins , 2006 .

[20]  M. A. Wouters,et al.  An analysis of side chain interactions and pair correlations within antiparallel β‐sheets: The differences between backbone hydrogen‐bonded and non‐hydrogen‐bonded residue pairs , 1995, Proteins.

[21]  K. Chou,et al.  Prediction of β-turns , 2009 .

[22]  J. Thornton,et al.  Prediction of strand pairing in antiparallel and parallel β‐sheets using information theory , 2002, Proteins.

[23]  Jens Meiler,et al.  Strand‐loop‐strand motifs: Prediction of hairpins and diverging turns in proteins , 2004, Proteins.

[24]  D. Baker,et al.  Coupled prediction of protein secondary and tertiary structure , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[25]  A. Cochran,et al.  Designing Stable β-Hairpins: Energetic Contributions from Cross-Strand Residues , 2000 .

[26]  François Major,et al.  Ranking the factors that contribute to protein beta-sheet folding. , 2007, Proteins.

[27]  M. Sternberg,et al.  The disulphide beta-cross: from cystine geometry and clustering to classification of small disulphide-rich protein folds. , 1996, Journal of molecular biology.

[28]  Amelia A. Fuller,et al.  A cross‐strand Trp–Trp pair stabilizes the hPin1 WW domain at the expense of function , 2007, Protein science : a publication of the Protein Society.

[29]  J. Thornton,et al.  Determinants of strand register in antiparallel β‐sheets of proteins , 1998, Protein science : a publication of the Protein Society.

[30]  Janet M Thornton,et al.  Toward predicting protein topology: an approach to identifying beta hairpins. , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[31]  C. Orengo,et al.  Correlation of observed fold frequency with the occurrence of local structural motifs. , 1999, Journal of molecular biology.

[32]  L. Gregoret,et al.  Context-dependence of amino acid residue pairing in antiparallel beta-sheets. , 1999, Journal of molecular biology.

[33]  Chih-Jen Lin,et al.  LIBSVM: A library for support vector machines , 2011, TIST.

[34]  Yael Mandel-Gutfreund,et al.  Contributions of residue pairing to β-sheet formation:conservation and covariation of amino acid residue pairs on antiparallel β-strands 1 1 Edited by J. Thornton , 2001 .

[35]  D. Baker,et al.  Design of a Novel Globular Protein Fold with Atomic-Level Accuracy , 2003, Science.