Application of 'inductive' QSAR descriptors for quantification of antibacterial activity of cationic polypeptides.

On the basis of the inductive QSAR descriptors we have created a neural network-based solution enabling quantification of antibacterial activity in the series of 101 synthetic cationic polypeptides (CAMEL-s). The developed QSAR model allowed 80% correct categorical classification of antibacterial potencies of the CAMEL-s both in the training and the validation sets. The accuracy of the activity predictions demonstrates that a narrow set of 3D sensitive 'inductive' descriptors can adequately describe the aspects of intra- and intermolecular interactions that are relevant for antibacterial activity of the cationic polypeptides. The developed approach can be further expanded for the larger sets of biologically active peptides and can serve as a useful quantitative tool for rational antibiotic design and discovery.

[1]  M. Zasloff,et al.  Anticancer efficacy of Magainin2 and analogue peptides. , 1993, Cancer research.

[2]  H. P. Fell,et al.  Structure-activity analysis of the antitumor and hemolytic properties of the amphiphilic alpha-helical peptide, C18G. , 2009, International journal of peptide and protein research.

[3]  E. Krause,et al.  Peptide helicity and membrane surface charge modulate the balance of electrostatic and hydrophobic interactions with lipid bilayers and biological membranes. , 1996, Biochemistry.

[4]  T. Auton,et al.  Design of active analogues of a 15-residue peptide using D-optimal design, QSAR and a combinatorial search algorithm. , 2009, The journal of peptide research : official journal of the American Peptide Society.

[5]  R. Hancock.  Peptide antibiotics , 1997, The Lancet.

[6]  D. Barra,et al.  Antimicrobial peptides from amphibian skin: what do they tell us? , 1998, Biopolymers.

[7]  Y. Shai,et al.  Mode of action of linear amphipathic α-helical antimicrobial peptides , 1998 .

[8]  R. García-Domenech,et al.  Antimicrobial Activity Characterization in a Heterogeneous Group of Compounds. , 1998 .

[9]  A. Engström,et al.  Antianaerobic activity of a cecropin---melittin peptide. , 1998, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[10]  H. Vogel,et al.  Structure-function relationships of antimicrobial peptides. , 1998, Biochemistry and cell biology = Biochimie et biologie cellulaire.

[11]  Artem Cherkasov,et al.  Substituent Effects on Thermochemical Properties of Free Radicals. New Substituent Scales for C-Centered Radicals , 1998, J. Chem. Inf. Comput. Sci..

[12]  R. Hancock,et al.  Cationic peptides: a new source of antibiotics. , 1998, Trends in biotechnology.

[13]  Artem Cherkasov,et al.  A NEW APPROACH TO THE THEORETICAL ESTIMATION OF INDUCTIVE CONSTANTS , 1998 .

[14]  H. Vogel,et al.  Diversity of antimicrobial peptides and their mechanisms of action. , 1999, Biochimica et biophysica acta.

[15]  R. Hancock,et al.  Peptide antibiotics , 1997, The Lancet.

[16]  Artem Cherkasov,et al.  “Inductive” electronegativity scale , 1999 .

[17]  Y. Shai,et al.  Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by alpha-helical antimicrobial and cell non-selective membrane-lytic peptides. , 1999, Biochimica et biophysica acta.

[18]  M. Dathe,et al.  Structural features of helical antimicrobial peptides: their potential to modulate activity on model membranes and biological cells. , 1999, Biochimica et biophysica acta.

[19]  A R Cherkasov,et al.  A novel approach to the analysis of substituent effects: quantitative description of ionization energies and gas basicity of amines. , 1999, Journal of molecular graphics & modelling.

[20]  Johann Gasteiger,et al.  Neural networks in chemistry and drug design , 1999 .

[21]  Artem Cherkasov,et al.  Substituent Effects on Thermochemical Properties of C-, N-, O-, and S-Centered Radicals. Physical Interpretation of Substituent Effects , 1999, J. Chem. Inf. Comput. Sci..

[22]  R. Cherkasov,et al.  Modelling of Substituents Electronic and Steric Effects for Effective Analysis of Organoelement and Organophosphorus Reactivity , 1999 .

[23]  S. Blondelle,et al.  Lipid-induced conformation and lipid-binding properties of cytolytic and antimicrobial peptides: determination and biological specificity. , 1999, Biochimica et biophysica acta.

[24]  B. Bechinger,et al.  The structure, dynamics and orientation of antimicrobial peptides in membranes by multidimensional solid-state NMR spectroscopy. , 1999, Biochimica et biophysica acta.

[25]  R. Lewis,et al.  The interaction of the antimicrobial peptide gramicidin S with lipid bilayer model and biological membranes. , 1999, Biochimica et biophysica acta.

[26]  B. Bechinger,et al.  The Interactions of Histidine-containing Amphipathic Helical Peptide Antibiotics with Lipid Bilayers , 1999, The Journal of Biological Chemistry.

[27]  R García-Domenech,et al.  Discovery of New Antimalarial Compounds by use of Molecular Connectivity Techniques , 1999, The Journal of pharmacy and pharmacology.

[28]  J. Jaén-Oltra,et al.  Artificial neural network applied to prediction of fluorquinolone antibacterial activity by topological methods. , 2000, Journal of medicinal chemistry.

[29]  F. Tomás-Vert,et al.  Artificial neural network applied to the discrimination of antibacterial activity by topological methods , 2000 .

[30]  Artem Cherkasov,et al.  “Inductive” electronegativity scale: 2. ‘Inductive’ analog of chemical hardness , 2000 .

[31]  H. Oh,et al.  Activities of Synthetic Hybrid Peptides against Anaerobic Bacteria: Aspects of Methodology and Stability , 2000, Antimicrobial Agents and Chemotherapy.

[32]  Artem Cherkasov,et al.  A New Method for Estimation of Homolytic C-H Bond Dissociation Enthalpies , 2000, J. Chem. Inf. Comput. Sci..

[33]  D. Barra,et al.  Involvement of Rel factors in the expression of antimicrobial peptide genes in amphibia. , 2001, European journal of biochemistry.

[34]  E J Park,et al.  Antibacterial, antitumor and hemolytic activities of alpha-helical antibiotic peptide, P18 and its analogs. , 2001, The journal of peptide research : official journal of the American Peptide Society.

[35]  Rama K. Mishra,et al.  Getting Discriminant Functions of Antibacterial Activity from Physicochemical and Topological Parameters , 2001, J. Chem. Inf. Comput. Sci..

[36]  B. Lemaître,et al.  Drosophila immunity: two paths to NF-κB , 2001 .

[37]  Mark T. D. Cronin,et al.  Structure-Based Classification of Antibacterial Activity , 2002, J. Chem. Inf. Comput. Sci..

[38]  Douglas M. Hawkins,et al.  Assessing Model Fit by Cross-Validation , 2003, J. Chem. Inf. Comput. Sci..

[39]  Artem Cherkasov,et al.  Inductive Electronegativity Scale. Iterative Calculation of Inductive Partial Charges , 2003, J. Chem. Inf. Comput. Sci..

[40]  A. Cherkasov,et al.  Three-Dimensional Correlation AnalysisA Novel Approach to the Quantification of Substituent Effects , 2003 .

[41]  S. Yonehara,et al.  Translocation of Analogues of the Antimicrobial Peptides Magainin and Buforin across Human Cell Membranes* , 2003, The Journal of Biological Chemistry.

[42]  G. Arenas,et al.  Antimicrobial peptides: A natural alternative to chemical antibiotics and a potential for applied biotechnology , 2003 .

[43]  R. Hancock.  Concerns regarding resistance to self-proteins. , 2003, Microbiology.

[44]  S. Gellman,et al.  Interactions of the antimicrobial β‐peptide β‐17 with phospholipid vesicles differ from membrane interactions of magainins , 2003 .

[45]  Maykel Pérez González,et al.  Designing Antibacterial Compounds Through a Topological Substructural Approach. , 2004 .

[46]  Artem Cherkasov.  Inductive QSAR Descriptors. Distinguishing Compounds with Antibacterial Activity by Artificial Neural Networks , 2005 .