Ab Initio SERVER PROTOTYPE FOR PREDICTION OF PHOSPHORYLATION SITES IN PROTEINS*
Plewczynski Dariusz, Rychlewski Leszek
BiolnfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan, Poland
darman@bioinfo.pl
Received:
Rec. 15 November 2003
DOI: 10.12921/cmst.2003.09.01.93-100
OAI: oai:lib.psnc.pl:554
Abstract:
We describe an ab initio server prototype for prediction of phosphorylation sites. A list
of possible active sites for a given query protein is build using query protein sequence and the database of proteins annotated for a certain type of activation process by Swiss-Prot DB. All short segments of a query protein sequence centered around plausible active sites are compared with experimental profiles. Those profiles describe both sequence and structure preferences for each type of active site. Prediction of local conformation of a query protein chain around examined site is done with the specially prepared library of short local structural segments (LSSs). The short sequence fragments from a query protein are matched with segments in the library using profile with profile alignment. Predicted local structure of a chain near active site qualitatively agrees with experimental data fetched from PDB database.
We estimate in this paper the level of improvement over purely sequence based methods gained by incorporating predicted structural information into the local description of phosphorylation sites.
References:
[1] M. Levitt, and M. Gerstein, A unified statistical framework for sequence comparison and structure comparison, Proc. Natl. Acad. Sci. 95, 5913-5920 (1998).
[2] R. Luthy, A. D. McLachlan, and D. Eisenberg, Secondary structure-based profiles: use of structure-conserving scoring tables within protein super families, Bioinformatics, 16, 1111-1119,
(1991).
[3] D. Fischer and D. Eisenberg, Protein fold recognition using sequence-derived predictions.
Protein Sci., 5, 947-955 (1996).
[4] H. Xu, R. Aurora, G. D, Rose, and R. H. White, Identifying two ancient enzymes in archaea
using predicted secondary structure alignment, Nature Structural Biology, 6, 750-754 (1999).
[5] L. Rychlewski, and A. Godzik, Secondary structure prediction using segment similarity. Protein Engineering, 10, 1143-1153 (1997).
[6] T. M. Yi, and E. S. Lander, Protein secondaiy structure prediction using nearest-neighbor
methods, J. Mol. Biol., 232, 1117-1129 (1993).
[7] C. Bystroff, and D. Baker, Prediction of local structure in proteins using a library of sequencestructure motifs, J. Mol. Biol., 281, 565-577 (1998).
[8] L. Rychlewski, M. Kschischo, L. Dong, M. Schutkowski, and U. Reimer, Target specificity
analysis of the Abl kinase using peptide microarray data, Submitted to JMB (2003).
[9] J. M. Chandonia, N, S. Walker, L. Lo Conte, P. Koehl, M. Levitt, and S. E. Brenner, ASTRAL
compendium enhancements, Nucleic Acids Research, 30, 260-263 (2002).
[10] S. E. Brenner, P. Koehl, and M. Levitt, The ASTRAL compendium for sequence and structure analysis, Nucleic Acids Research 28, 254-256 (2000).
[11] S. F. Altschul. W. Gish, W. Miller, E. W. Myers, and D. J. Lipman, Basic local alignment search
tool, J. Mol. Biol., 215, 403-410 (1990).
[12] S. F. Altschul, T. L. Madden, A. A. Schäffer, J. Zhang, Z. Zhang, W. Miller, and D. J. Lipman,
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25, 3389-3402 (1997).
[13] L. Rychlewski, L. Jaroszewski, W. Li, A. Godzik, Comparison of sequence profdes. Strategies for structural predictions using sequence information, Protein Science, 9, 232-241 (2000).
[14] L. Jaroszewski, W. Li, and A. Godzik, Improving the quality of twilight-zone alignments, Prot. Sci., 9, 1487-1496 (2001).
[15] R. Linding, R. B. Russell, V. Neduva, and T. J. Gibson, GlobPlot: exploring protein sequences
for globularity and disorder. Nucleic Acids Research. 31. 3701-3708 (2003).
We describe an ab initio server prototype for prediction of phosphorylation sites. A list
of possible active sites for a given query protein is build using query protein sequence and the database of proteins annotated for a certain type of activation process by Swiss-Prot DB. All short segments of a query protein sequence centered around plausible active sites are compared with experimental profiles. Those profiles describe both sequence and structure preferences for each type of active site. Prediction of local conformation of a query protein chain around examined site is done with the specially prepared library of short local structural segments (LSSs). The short sequence fragments from a query protein are matched with segments in the library using profile with profile alignment. Predicted local structure of a chain near active site qualitatively agrees with experimental data fetched from PDB database.
We estimate in this paper the level of improvement over purely sequence based methods gained by incorporating predicted structural information into the local description of phosphorylation sites.
[1] M. Levitt, and M. Gerstein, A unified statistical framework for sequence comparison and structure comparison, Proc. Natl. Acad. Sci. 95, 5913-5920 (1998).
[2] R. Luthy, A. D. McLachlan, and D. Eisenberg, Secondary structure-based profiles: use of structure-conserving scoring tables within protein super families, Bioinformatics, 16, 1111-1119,
(1991).
[3] D. Fischer and D. Eisenberg, Protein fold recognition using sequence-derived predictions.
Protein Sci., 5, 947-955 (1996).
[4] H. Xu, R. Aurora, G. D, Rose, and R. H. White, Identifying two ancient enzymes in archaea
using predicted secondary structure alignment, Nature Structural Biology, 6, 750-754 (1999).
[5] L. Rychlewski, and A. Godzik, Secondary structure prediction using segment similarity. Protein Engineering, 10, 1143-1153 (1997).
[6] T. M. Yi, and E. S. Lander, Protein secondaiy structure prediction using nearest-neighbor
methods, J. Mol. Biol., 232, 1117-1129 (1993).
[7] C. Bystroff, and D. Baker, Prediction of local structure in proteins using a library of sequencestructure motifs, J. Mol. Biol., 281, 565-577 (1998).
[8] L. Rychlewski, M. Kschischo, L. Dong, M. Schutkowski, and U. Reimer, Target specificity
analysis of the Abl kinase using peptide microarray data, Submitted to JMB (2003).
[9] J. M. Chandonia, N, S. Walker, L. Lo Conte, P. Koehl, M. Levitt, and S. E. Brenner, ASTRAL
compendium enhancements, Nucleic Acids Research, 30, 260-263 (2002).
[10] S. E. Brenner, P. Koehl, and M. Levitt, The ASTRAL compendium for sequence and structure analysis, Nucleic Acids Research 28, 254-256 (2000).
[11] S. F. Altschul. W. Gish, W. Miller, E. W. Myers, and D. J. Lipman, Basic local alignment search
tool, J. Mol. Biol., 215, 403-410 (1990).
[12] S. F. Altschul, T. L. Madden, A. A. Schäffer, J. Zhang, Z. Zhang, W. Miller, and D. J. Lipman,
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res. 25, 3389-3402 (1997).
[13] L. Rychlewski, L. Jaroszewski, W. Li, A. Godzik, Comparison of sequence profdes. Strategies for structural predictions using sequence information, Protein Science, 9, 232-241 (2000).
[14] L. Jaroszewski, W. Li, and A. Godzik, Improving the quality of twilight-zone alignments, Prot. Sci., 9, 1487-1496 (2001).
[15] R. Linding, R. B. Russell, V. Neduva, and T. J. Gibson, GlobPlot: exploring protein sequences
for globularity and disorder. Nucleic Acids Research. 31. 3701-3708 (2003).
