Analysis of Protein Protein Dimeric Interfaces

We analyzed the structural properties and the local surface environment of surface amino acid residues of proteins using a large, non-redundant dataset of 2383 protein chains in dimeric complexes from PDB. We compared the interface residues and non-interface residues based on six properties: side chain orientation, surface roughness, solid angle, ex value, hydrophobicity and interface cluster size. The results of our analysis show that interface residues have side chains pointing inward; interfaces are rougher, tend to be flat, moderately convex or concave and protrude more relative to non-interface surface residues. Interface residues tend to be surrounded by hydrophobic neighbors and tend to form clusters consisting of three or more interfaces residues. These findings are consistent with previous published studies using much smaller datasets, while allowing for more qualitative conclusions due to our larger dataset. Preliminary results suggest the possibility of using the six the properties to identify putative interface residues.

[1]  Huan-Xiang Zhou,et al.  Interaction-site prediction for protein complexes: a critical assessment , 2007, Bioinform..

[2]  Naonori Ueda,et al.  Parametric Mixture Models for Multi-Labeled Text , 2002, NIPS.

[3]  M. L. Connolly.  Solvent-accessible surfaces of proteins and nucleic acids. , 1983, Science.

[4]  R. Jernigan,et al.  How do side chains orient globally in protein structures? , 2005, Proteins.

[5]  J. Skolnick,et al.  Prediction of physical protein–protein interactions , 2005, Physical biology.

[6]  S. Rackovsky,et al.  Hydrophobicity, hydrophilicity, and the radial and orientational distributions of residues in native proteins. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[7]  D. Covell,et al.  A role for surface hydrophobicity in protein‐protein recognition , 1994, Protein science : a publication of the Protein Society.

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

[9]  M. L. Connolly.  Measurement of protein surface shape by solid angles , 1986 .

[10]  A M Lesk,et al.  Interior and surface of monomeric proteins. , 1987, Journal of molecular biology.

[11]  J. Thornton,et al.  PQS: a protein quaternary structure file server. , 1998, Trends in biochemical sciences.

[12]  Oliviero Carugo,et al.  CX, an algorithm that identifies protruding atoms in proteins , 2002, Bioinform..

[13]  K. Bretonnel Cohen,et al.  A shared task involving multi-label classification of clinical free text , 2007, BioNLP@ACL.

[14]  Susan T. Dumais,et al.  Inductive learning algorithms and representations for text categorization , 1998, CIKM '98.

[15]  S. Jones,et al.  Analysis of protein-protein interaction sites using surface patches. , 1997, Journal of molecular biology.

[16]  Vasant Honavar,et al.  A two-stage classifier for identification of protein-protein interface residues , 2004, ISMB/ECCB.

[17]  Thorsten Joachims,et al.  Text Categorization with Support Vector Machines: Learning with Many Relevant Features , 1998, ECML.

[18]  B. Lee,et al.  The interpretation of protein structures: estimation of static accessibility. , 1971, Journal of molecular biology.

[19]  Benjamin A. Shoemaker,et al.  Deciphering Protein–Protein Interactions. Part II. Computational Methods to Predict Protein and Domain Interaction Partners , 2007, PLoS Comput. Biol..

[20]  Vladimir Vapnik,et al.  The Nature of Statistical Learning , 1995 .

[21]  B. Rost,et al.  Analysing six types of protein-protein interfaces. , 2003, Journal of molecular biology.

[22]  Vasant Honavar,et al.  Characterization of Protein–Protein Interfaces , 2008, The protein journal.

[23]  Frank K. Pettit,et al.  Protein surface roughness and small molecular binding sites. , 1999, Journal of molecular biology.

[24]  A. Bogan,et al.  Anatomy of hot spots in protein interfaces. , 1998, Journal of molecular biology.

[25]  Yihong Gong,et al.  Multi-labelled classification using maximum entropy method , 2005, SIGIR '05.

[26]  M L Connolly,et al.  The molecular surface package. , 1993, Journal of molecular graphics.

[27]  M. Lewis,et al.  Fractal surfaces of proteins. , 1985, Science.

[28]  Yoram Singer,et al.  BoosTexter: A Boosting-based System for Text Categorization , 2000, Machine Learning.

[29]  A. Bulpitt,et al.  Insights into protein-protein interfaces using a Bayesian network prediction method. , 2006, Journal of molecular biology.

[30]  D. Eisenberg,et al.  Three-dimensional cluster analysis identifies interfaces and functional residue clusters in proteins. , 2001, Journal of molecular biology.

[31]  Fabrizio Sebastiani,et al.  Machine learning in automated text categorization , 2001, CSUR.

[32]  Sophia Ananiadou,et al.  The C-value/NC-value domain-independent method for multi-word term extraction , 1999 .

[33]  Benjamin A. Shoemaker,et al.  Deciphering Protein–Protein Interactions. Part I. Experimental Techniques and Databases , 2007, PLoS Comput. Biol..

[34]  Naftali Tishby,et al.  ProMateus—an open research approach to protein-binding sites analysis , 2007, Nucleic Acids Res..

[35]  Susan Jones,et al.  SHARP2: protein-protein interaction predictions using patch analysis , 2006, Bioinform..