Alignment of Non-Covalent Interactions at Protein-Protein Interfaces

Background The study and comparison of protein-protein interfaces is essential for the understanding of the mechanisms of interaction between proteins. While there are many methods for comparing protein structures and protein binding sites, so far no methods have been reported for comparing the geometry of non-covalent interactions occurring at protein-protein interfaces. Methodology/Principal Findings Here we present a method for aligning non-covalent interactions between different protein-protein interfaces. The method aligns the vector representations of van der Waals interactions and hydrogen bonds based on their geometry. The method has been applied to a dataset which comprises a variety of protein-protein interfaces. The alignments are consistent to a large extent with the results obtained using two other complementary approaches. In addition, we apply the method to three examples of protein mimicry. The method successfully aligns respective interfaces and allows for recognizing conserved interface regions. Conclusions/Significance The Galinter method has been validated in the comparison of interfaces in which homologous subunits are involved, including cases of mimicry. The method is also applicable to comparing interfaces involving non-peptidic compounds. Galinter assists users in identifying local interface regions with similar patterns of non-covalent interactions. This is particularly relevant to the investigation of the molecular basis of interaction mimicry.

[1]  P. Sparén,et al.  Efficiency of organised and opportunistic cytological screening for cancer in situ of the cervix , 1995, British Journal of Cancer.

[2]  J M Thornton,et al.  Derivation of 3D coordinate templates for searching structural databases: Application to ser‐His‐Asp catalytic triads in the serine proteinases and lipases , 1996, Protein science : a publication of the Protein Society.

[3]  H. Wolfson,et al.  A dataset of protein-protein interfaces generated with a sequence-order-independent comparison technique. , 1996, Journal of molecular biology.

[4]  François Stricher,et al.  Scorpion-toxin mimics of CD4 in complex with human immunodeficiency virus gp120 crystal structures, molecular mimicry, and neutralization breadth. , 2005, Structure.

[5]  Michael Schroeder,et al.  SCOPPI: a structural classification of protein–protein interfaces , 2005, Nucleic Acids Res..

[6]  A G Murzin,et al.  SCOP: a structural classification of proteins database for the investigation of sequences and structures. , 1995, Journal of molecular biology.

[7]  R. Nussinov,et al.  Favorable scaffolds: proteins with different sequence, structure and function may associate in similar ways. , 2005, Protein engineering, design & selection : PEDS.

[8]  J. Thornton,et al.  Diversity of protein–protein interactions , 2003, The EMBO journal.

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

[10]  Ozlem Keskin,et al.  Similar binding sites and different partners: implications to shared proteins in cellular pathways. , 2007, Structure.

[11]  J. Janin,et al.  A dissection of specific and non-specific protein-protein interfaces. , 2004, Journal of molecular biology.

[12]  C. Bron,et al.  Algorithm 457: finding all cliques of an undirected graph , 1973 .

[13]  Z. Deng,et al.  Structural interaction fingerprint (SIFt): a novel method for analyzing three-dimensional protein-ligand binding interactions. , 2004, Journal of medicinal chemistry.

[14]  Christopher D. Thanos,et al.  Hot-spot mimicry of a cytokine receptor by a small molecule , 2006, Proceedings of the National Academy of Sciences.

[15]  H. Wolfson,et al.  A new, structurally nonredundant, diverse data set of protein–protein interfaces and its implications , 2004, Protein science : a publication of the Protein Society.

[16]  Z. Weng,et al.  Structure, function, and evolution of transient and obligate protein-protein interactions. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[17]  F. Young.  Biochemistry , 1955, The Indian Medical Gazette.

[18]  P Willett,et al.  Identification of tertiary structure resemblance in proteins using a maximal common subgraph isomorphism algorithm. , 1993, Journal of molecular biology.

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

[20]  Meitian Wang,et al.  Crystal Structures of the RNA-dependent RNA Polymerase Genotype 2a of Hepatitis C Virus Reveal Two Conformations and Suggest Mechanisms of Inhibition by Non-nucleoside Inhibitors* , 2005, Journal of Biological Chemistry.

[21]  L. Polgár.  The catalytic triad of serine peptidases , 2005, Cellular and Molecular Life Sciences CMLS.

[22]  Ruth Nussinov,et al.  Protein-Protein Interfaces: Recognition of Similar Spatial and Chemical Organizations , 2004, WABI.

[23]  Liskin Swint-Kruse,et al.  Resmap: automated representation of macromolecular interfaces as two-dimensional networks , 2005, Bioinform..

[24]  R. Norel,et al.  Electrostatic aspects of protein-protein interactions. , 2000, Current opinion in structural biology.

[25]  Sarah A. Teichmann,et al.  Principles of protein-protein interactions , 2002, ECCB.

[26]  J. Richardson,et al.  Asparagine and glutamine: using hydrogen atom contacts in the choice of side-chain amide orientation. , 1999, Journal of molecular biology.

[27]  Thomas Lengauer,et al.  An Algorithm for Finding Maximal Common Subtopologies in a Set of Protein Structures , 1996, J. Comput. Biol..

[28]  Michael Schroeder,et al.  Equivalent binding sites reveal convergently evolved interaction motifs , 2006, Bioinform..

[29]  G. Klebe,et al.  A new method to detect related function among proteins independent of sequence and fold homology. , 2002, Journal of molecular biology.

[30]  Hongbo Zhu,et al.  NOXclass: prediction of protein-protein interaction types , 2006, BMC Bioinformatics.

[31]  G. Levi.  A note on the derivation of maximal common subgraphs of two directed or undirected graphs , 1973 .

[32]  Ruth Nussinov,et al.  MAPPIS: Multiple 3D Alignment of Protein-Protein Interfaces , 2005, CompLife.

[33]  Janet M. Thornton,et al.  Analysis of binding site similarity, small-molecule similarity and experimental binding profiles in the human cytosolic sulfotransferase family , 2007, Bioinform..

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

[35]  M. Randal,et al.  Potent small-molecule binding to a dynamic hot spot on IL-2. , 2003, Journal of the American Chemical Society.

[36]  W. Delano.  The PyMOL Molecular Graphics System , 2002 .

[37]  R. Russell,et al.  The relationship between sequence and interaction divergence in proteins. , 2003, Journal of molecular biology.

[38]  R. Nussinov,et al.  Hydrogen bonds and salt bridges across protein-protein interfaces. , 1997, Protein engineering.

[39]  Philip E. Bourne,et al.  The Protein Data Bank, 1999– , 2006 .

[40]  Thomas Lengauer,et al.  Inferring Protein Function from Protein Structure , 2007 .

[41]  L. Swint-Kruse.  Using networks to identify fine structural differences between functionally distinct protein states. , 2004, Biochemistry.

[42]  Ruth Nussinov,et al.  Generation and analysis of a protein–protein interface data set with similar chemical and spatial patterns of interactions , 2005, Proteins.

[43]  Liisa Holm,et al.  DaliLite workbench for protein structure comparison , 2000, Bioinform..

[44]  C. Chothia,et al.  The atomic structure of protein-protein recognition sites. , 1999, Journal of molecular biology.

[45]  H. Wolfson,et al.  Spatial chemical conservation of hot spot interactions in protein-protein complexes , 2007, BMC Biology.

[46]  Pinak Chakrabarti,et al.  Hydration of protein–protein interfaces , 2005, Proteins.