A Fast and Simple Approach to Computational Peptidology


Therapeutic peptides derived from natural marine products exhibit great potential for the treatment of numerous diseases. Thus, it is of best interest to extensively research and understand their molecular properties and bioactivity. From a molecular perspective, researchers have recently established that their bioactivity is related to their chemical reactivity in one way or the other. This has presented more opportunities for researchers to predict molecules’ interactions and understand the chemical reactions between them.

In a recent paper published in the research journal Chemical Physics Letters, Professor Norma Flores-Holguín and Professor Daniel Glossman-Mitnik from Centro de Investigación en Materiales Avanzados in Mexico together with Professor Juan Frau from University of the Balearic Islands in Spain particularly investigated the chemical reactivity of Pristinamycin, a family of antimicrobial peptides, using Conceptual Density Functional Theory (DFT). These concepts in conjunction with the Parr function were used to determine the global and local properties of the peptide necessary for prediction of the active reaction sites.

The reactivity and bioactivity of several compounds have been related based on the DFT concepts. Chemical reactivity of four-member groups of Pristinamycin family of antimicrobial peptides: Pristinamycin IA, Pristinamycin IB, Pristinamycin IIA, and Pristinamycin IIB was evaluated. Based on the chemical hardness values obtained in their previous results, the authors accurately predicted the pKa values of all the individual therapeutic peptides. In addition, the simple methodology successfully distinguished the pKa value of every individual peptide regardless of them having very small differences. It is worth noting that the information from their previous results was useful not only in understanding the chemical reactivity of the peptide but also their solubility in water, and equally important property in their practical applications.

Active reaction sites for both electrophilic and nucleophilic regions were established due to better behavior of the Parr functions. Based on the determined electrophilicity index ω and nucleophilicity index N, it was possible to classify the studied Pristinamycin peptides in different scales as proposed in the literature. Even though all the 4 members were observed to exhibit strong electrophilic properties, only Pristinamycin IIA and IIB exhibited moderate nucelophilic behavior while Pristinamycin IA and IB were regarded as strong nucelophiles.

In summary, a simple methodology for evaluation of the chemical reactivity properties of Pristinamycin peptides based on Conceptual DFT techniques is presented. Their study highlights new insight in understanding the chemical reactivity properties of Pristinamycin molecules that can be used in further exploration of peptides reactivity as well as understanding the toxicity mechanisms associated with them. Furthermore, the research team proved that the presented approach can be used to accurately predict the pKa values of different peptides which can provide useful information for the design and development of new pharmaceutical drugs.

A Fast and Simple Approach to Computational Peptidology - Advances in Engineering

About the author

Dra. Norma Rosario Flores Holguín is now an Academic technician level C, at Advanced Materials Research Center (CIMAV), Chihuahua, México. Also is a Researcher Level 1 in National Research System of National Council of Science and Technology (CONACYT).

Her academic interest are Molecular modeling and computational chemistry with applications on Photovoltaic Solar Cells, drug designs and computational nanochemistry. She has authored a coauthored 76 peer-reviewed papers and 8 book chapters. She has delivered speeches in international and domestic conferences and serves as referee for more than 26 international journals.

About the author

Dr. Daniel Glossman-Mitnik is now a Titular Researcher at the Centro de Investigación en Materiales Avanzados (CIMAV), Chihuahua, Mexico as well as a National Researcher of Level III of the Consejo Nacional de Ciencia y Tecnología, Mexico. His research interest focuses on Computational Chemistry and Molecular Modeling of molecular systems of pharmacological, food and alternative energy interests by resorting to DFT and Conceptual DFT.

He has authored a coauthored more that 230 peer-reviewed papers, 15 book chapters and 2 edited books. He has delivered speeches in many international and domestic conferences. He serves as the referee for more than 60 international journals, books and research proposals.

About the author

Dr. Juan Frau is a full professor at University of Balearic Islands (Palma de Mallorca, Spain). The main lines of research are related to the study of biological systems, as lactam compounds, vitamin B6 derivatives and non-enzymatic protein glycation, using Computational Chemistry Techniques, as molecular dynamic simulations, Conceptual DFT and 3D-QSAR.

He is author of more than 110 peer-reviewed papers and has participated in more than 30 research projects. Director of four doctoral theses and ten master’s theses. He has been a member of the organizing committee, the scientific committee or the executive board of scientific congresses as VI Electronic Structure: Principles and Applications, Glycoproteins congress: From structure to disease, 6th EuCheMS Chemistry Congress.


Flores-Holguín, N., Frau, J., & Glossman-Mitnik, D. (2020). A Fast and Simple Evaluation of the Chemical Reactivity Properties of the Pristinamycin Family of Antimicrobial Peptides. Chemical Physics Letters, 739, 137021.

Go To Chemical Physics Letters

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