TY - JOUR

T1 - QSAR modeling of the antimicrobial activity of peptides as a mathematical function of a sequence of amino acids

AU - Toropova, Mariya A.

AU - Veselinović, Aleksandar M.

AU - Veselinović, Jovana B.

AU - Stojanović, Dušica B.

AU - Toropov, Andrey A.

PY - 2015/12/1

Y1 - 2015/12/1

N2 - Antimicrobial peptides have emerged as new therapeutic agents for fighting multi-drug-resistant bacteria. However, the process of optimizing peptide antimicrobial activity and specificity using large peptide libraries is both tedious and expensive. Therefore, computational techniques had to be applied for process optimization. In this work, the representation of the molecular structure of peptides (mastoparan analogs) by a sequence of amino acids has been used to establish quantitative structure - activity relationships (QSARs) for their antibacterial activity. The data for the studied peptides were split three times into the training, calibration and test sets. The Monte Carlo method was used as a computational technique for QSAR models calculation. The statistical quality of QSAR for the antibacterial activity of peptides for the external validation set was: n = 7, r2 = 0.8067, s = 0.248 (split 1); n = 6, r2 = 0.8319, s = 0.169 (split 2); and n = 6, r2 = 0.6996, s = 0.297 (split 3). The stated statistical parameters favor the presented QSAR models in comparison to 2D and 3D descriptor based ones. The Monte Carlo method gave a reasonably good prediction for the antibacterial activity of peptides. The statistical quality of the prediction is different for three random splits. However, the predictive potential is reasonably well for all cases. The presented QSAR modeling approach can be an attractive alternative of 3D QSAR at least for the described peptides.

AB - Antimicrobial peptides have emerged as new therapeutic agents for fighting multi-drug-resistant bacteria. However, the process of optimizing peptide antimicrobial activity and specificity using large peptide libraries is both tedious and expensive. Therefore, computational techniques had to be applied for process optimization. In this work, the representation of the molecular structure of peptides (mastoparan analogs) by a sequence of amino acids has been used to establish quantitative structure - activity relationships (QSARs) for their antibacterial activity. The data for the studied peptides were split three times into the training, calibration and test sets. The Monte Carlo method was used as a computational technique for QSAR models calculation. The statistical quality of QSAR for the antibacterial activity of peptides for the external validation set was: n = 7, r2 = 0.8067, s = 0.248 (split 1); n = 6, r2 = 0.8319, s = 0.169 (split 2); and n = 6, r2 = 0.6996, s = 0.297 (split 3). The stated statistical parameters favor the presented QSAR models in comparison to 2D and 3D descriptor based ones. The Monte Carlo method gave a reasonably good prediction for the antibacterial activity of peptides. The statistical quality of the prediction is different for three random splits. However, the predictive potential is reasonably well for all cases. The presented QSAR modeling approach can be an attractive alternative of 3D QSAR at least for the described peptides.

KW - Antimicrobial activity

KW - CORAL software

KW - Mastoparan analogs

KW - Monte Carlo method

KW - Optimal descriptor

KW - QSAR

UR - http://www.scopus.com/inward/record.url?scp=84944033060&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84944033060&partnerID=8YFLogxK

U2 - 10.1016/j.compbiolchem.2015.09.009

DO - 10.1016/j.compbiolchem.2015.09.009

M3 - Article

C2 - 26454621

AN - SCOPUS:84944033060

VL - 59

SP - 126

EP - 130

JO - Computational Biology and Chemistry

JF - Computational Biology and Chemistry

SN - 1476-9271

ER -