Monatshefte für Chemie - Chemical Monthly

, Volume 143, Issue 4, pp 535–543 | Cite as

Prediction of improved antimicrobial mastoparan derivatives by 3D-QSAR-CoMSIA/CoMFA and computational mutagenesis

  • Speranta Avram
  • Dan Mihailescu
  • Florin Borcan
  • Adina-Luminita MilacEmail author
Original Paper


Antimicrobial peptides are an important class of therapeutic agents used against a wide range of pathogens such as gram-negative and -positive bacteria, fungi, and viruses. The minimal inhibitory concentration at the level of the pathogen membrane is a major determinant of the pharmacokinetic behavior and, consequently, it can affect their antimicrobial activity. Here we generated quantitative structure-activity relationship models (3D-QSAR—comparative molecular field analysis/comparative molecular similarity indices analysis) using a database of 33 mastoparan analogs, antimicrobial peptides with known experimental activity, and further used these models to predict the minimal inhibitory concentration for 18 new mastoparan analogs, obtained by computational mutagenesis. We discuss two options for structural alignment of mastoparan analogs: superposition of Cα trace atoms or superposition of all backbone atoms. Significant values of the cross-validated correlation q 2 (higher than 0.60) and the fitted correlation r 2 (higher than 0.90) of our models indicate that they are reliable enough for activity prediction in the case of new derivatives. This allows us to identify compounds with possibly enhanced antimicrobial activity against Bacillus subtilis, which are suggested for further experimental studies.

Graphical Abstract


Mastoparan analogs Drug research Peptides QSAR Computational mutagenesis 



We acknowledge the financial support of CNMP PNII 61-016/2007, CNMP PNII 62-061/2008, and PNII PD-586/2010. A.-L. Milac was supported by the Romanian Academy project 3 of the Institute of Biochemistry of the Romanian Academy. A.-L. Milac acknowledges the postdoctoral program POSDRU/89/1.5/S/60746 from the European Social Fund.


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Speranta Avram
    • 2
  • Dan Mihailescu
    • 2
  • Florin Borcan
    • 3
  • Adina-Luminita Milac
    • 1
    Email author
  1. 1.Institute of Biochemistry of the Romanian AcademyBucharestRomania
  2. 2.Faculty of Biology, Anatomy, Animal Physiology and Biophysics DepartmentUniversity of BucharestBucharestRomania
  3. 3.Pharmaceutical Chemistry Department, Faculty of Pharmacy“Victor Babes” University of Medicine and PharmacyTimisoaraRomania

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