Analysis and Prediction of Highly Effective Antiviral Peptides Based on Random Forests

The goal of this study was to examine and predict antiviral peptides. Although antiviral peptides hold great potential in antiviral drug discovery, little is done in antiviral peptide prediction. In this study, we demonstrate that a physicochemical model using random forests outperform in distinguishing antiviral peptides. On the experimental benchmark, our physicochemical model aided with aggregation and secondary structural features reaches 90% accuracy and 0.79 Matthew's correlation coefficient, which exceeds the previous models. The results suggest that aggregation could be an important feature for identifying antiviral peptides. In addition, our analysis reveals the characteristics of the antiviral peptides such as the importance of lysine and the abundance of α-helical secondary structures.

[1]  M. Wainberg Perspectives on antiviral drug development. , 2009, Antiviral research.

[2]  M. Kumar,et al.  HIPdb: A Database of Experimentally Validated HIV Inhibiting Peptides , 2013, PloS one.

[3]  Guillaume Castel,et al.  Phage Display of Combinatorial Peptide Libraries: Application to Antiviral Research , 2011, Molecules.

[4]  Manoj Kumar,et al.  AVPpred: collection and prediction of highly effective antiviral peptides , 2012, Nucleic Acids Res..

[5]  Yong-tang Zheng,et al.  Current Peptide HIV Type-1 Fusion Inhibitors , 2009, Antiviral chemistry & chemotherapy.

[6]  Tin Kam Ho,et al.  The Random Subspace Method for Constructing Decision Forests , 1998, IEEE Trans. Pattern Anal. Mach. Intell..

[7]  Rich Caruana,et al.  An empirical evaluation of supervised learning in high dimensions , 2008, ICML '08.

[8]  Andrew J. Wilson,et al.  Inhibition of α-helix-mediated protein-protein interactions using designed molecules. , 2013, Nature chemistry.

[9]  M. Dalakas,et al.  Mitochondrial toxicity of antiviral drugs , 1995, Nature Medicine.

[10]  G. Schneider,et al.  Designing antimicrobial peptides: form follows function , 2011, Nature Reviews Drug Discovery.

[11]  K. Chou,et al.  Prediction of Antimicrobial Peptides Based on Sequence Alignment and Feature Selection Methods , 2011, PloS one.

[12]  T. Matsui,et al.  Inhibitory effect of 2',3'-didehydro-2',3'-dideoxynucleosides on infectivity, cytopathic effects, and replication of human immunodeficiency virus , 1987, Antimicrobial Agents and Chemotherapy.

[13]  Hiroyuki Ogata,et al.  AAindex: Amino Acid Index Database , 1999, Nucleic Acids Res..

[14]  T. Matthews,et al.  Design of helical, oligomeric HIV-1 fusion inhibitor peptides with potent activity against enfuvirtide-resistant virus , 2007, Proceedings of the National Academy of Sciences.

[15]  C. Brandt,et al.  Multiple Peptides Homologous to Herpes Simplex Virus Type 1 Glycoprotein B Inhibit Viral Infection , 2008, Antimicrobial Agents and Chemotherapy.

[16]  Jeremy C. Jones,et al.  Identification of the Minimal Active Sequence of an Anti-Influenza Virus Peptide , 2011, Antimicrobial Agents and Chemotherapy.

[17]  Shreyas Karnik,et al.  CAMP: a useful resource for research on antimicrobial peptides , 2009, Nucleic Acids Res..

[18]  Andy Liaw,et al.  Classification and Regression by randomForest , 2007 .

[19]  P. Legrain,et al.  Antiviral Drug Discovery Strategy Using Combinatorial Libraries of Structurally Constrained Peptides , 2004, Journal of Virology.

[20]  J. Drummond,et al.  Design and optimization of a multiplex anti-influenza peptide immunoassay. , 2008, Journal of immunological methods.

[21]  R D Appel,et al.  Protein identification and analysis tools in the ExPASy server. , 1999, Methods in molecular biology.

[22]  Fuhui Long,et al.  Feature selection based on mutual information criteria of max-dependency, max-relevance, and min-redundancy , 2003, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[23]  R. Schinazi,et al.  Potent and selective in vitro activity of 3'-deoxythymidin-2'-ene (3'-deoxy-2',3'-didehydrothymidine) against human immunodeficiency virus. , 1987, Biochemical pharmacology.

[24]  M. García-Delgado,et al.  Peptide Inhibitors of Hepatitis C Virus NS3 Protease , 2003, Antiviral chemistry & chemotherapy.

[25]  R. Hancock,et al.  The role of cationic antimicrobial peptides in innate host defences. , 2000, Trends in microbiology.

[26]  Marc Torrent,et al.  Connecting Peptide Physicochemical and Antimicrobial Properties by a Rational Prediction Model , 2011, PloS one.

[27]  J. Louis,et al.  Hydrophilic peptides derived from the transframe region of Gag-Pol inhibit the HIV-1 protease. , 1998, Biochemistry.

[28]  D. J. Bauer,et al.  9-(2-Hydroxyethoxymethyl)guanine activity against viruses of the herpes group , 1978, Nature.

[29]  Yang Zhang,et al.  I-TASSER server for protein 3D structure prediction , 2008, BMC Bioinformatics.

[30]  Leo Breiman,et al.  Random Forests , 2001, Machine Learning.

[31]  Gajendra P. S. Raghava,et al.  AntiBP2: improved version of antibacterial peptide prediction , 2010, BMC Bioinformatics.

[32]  R. Frank,et al.  Identification of High-Affinity PB1-Derived Peptides with Enhanced Affinity to the PA Protein of Influenza A Virus Polymerase , 2010, Antimicrobial Agents and Chemotherapy.

[33]  M. W. Pandit,et al.  Correlation between stability of a protein and its dipeptide composition: a novel approach for predicting in vivo stability of a protein from its primary sequence. , 1990, Protein engineering.

[34]  Alon Herschhorn,et al.  Inhibition of the activities of reverse transcriptase and integrase of human immunodeficiency virus type-1 by peptides derived from the homologous viral protein R (Vpr). , 2007, Journal of molecular biology.

[35]  D W Barry,et al.  3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Gisbert Schneider,et al.  Designing antimicrobial peptides: form follows function , 2012, Nature Reviews Drug Discovery.

[37]  Ashish,et al.  Antiviral Peptides Targeting the West Nile Virus Envelope Protein , 2006, Journal of Virology.

[38]  K. M. Hwang,et al.  Peptides Derived from the CDR3‐Homologous Domain of the CD4 Molecule Are Specific Inhibitors of HIV‐1 and SIV Infection, Virus‐Induced Cell Fusion, and Postinfection Viral Transmission in Vitro , 1990, Annals of the New York Academy of Sciences.

[39]  Francesc X. Avilés,et al.  AGGRESCAN: a server for the prediction and evaluation of "hot spots" of aggregation in polypeptides , 2007, BMC Bioinform..

[40]  E. De Clercq,et al.  Oral (E)-5-(2-bromovinyl)-2'-deoxyuridine in severe herpes zoster. , 1980, British medical journal.

[41]  R. Doolittle,et al.  A simple method for displaying the hydropathic character of a protein. , 1982, Journal of molecular biology.

[42]  Víctor Urrea,et al.  Letter to the Editor: Stability of Random Forest importance measures , 2011, Briefings Bioinform..

[43]  T. H. Rider,et al.  Broad-Spectrum Antiviral Therapeutics , 2011, PloS one.

[44]  A Ikai,et al.  Thermostability and aliphatic index of globular proteins. , 1980, Journal of biochemistry.

[45]  P. Anderson,et al.  L-743, 726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase , 1995, Antimicrobial agents and chemotherapy.

[46]  J Desmyter,et al.  Both 2',3'-dideoxythymidine and its 2',3'-unsaturated derivative (2',3'-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro. , 1987, Biochemical and biophysical research communications.

[47]  T. Matthews,et al.  A synthetic peptide from HIV-1 gp41 is a potent inhibitor of virus-mediated cell-cell fusion. , 1993, AIDS research and human retroviruses.

[48]  Leo Breiman,et al.  Bagging Predictors , 1996, Machine Learning.

[49]  Alon Herschhorn,et al.  Peptides Derived from the Reverse Transcriptase of Human Immunodeficiency Virus Type 1 as Novel Inhibitors of the Viral Integrase* , 2005, Journal of Biological Chemistry.

[50]  E. Clercq A 40-Year Journey in Search of Selective Antiviral Chemotherapy* , 2011 .