Insights into the Adsorption Mechanisms of the Antimicrobial Peptide CIDEM-501 on Membrane Models

Author:

Alpízar-Pedraza Daniel1ORCID,Roque-Diaz Yessica12ORCID,Garay-Pérez Hilda3ORCID,Rosenau Frank4ORCID,Ständker Ludger5ORCID,Montero-Alejo Vivian1ORCID

Affiliation:

1. Biochemistry and Molecular Biology Department, Center for Pharmaceutical Research and Development, Ave. 26 # 1605, Nuevo Vedado, Ciudad de La Habana 10400, Cuba

2. Department of Life and Environmental Sciences, Polytechnic University of Marche, Via Brecce Bianche, 12, 60131 Ancona, Italy

3. Peptide Synthesis Group, Center for Genetic Engineering and Biotechnology, Ave. 31 e/158 y 190, Playa, Habana 11600, Cuba

4. Institute of Pharmaceutical Biotechnology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany

5. Core Facility for Functional Peptidomics, Ulm Peptide Pharmaceuticals (U-PEP), Faculty of Medicine, Ulm University, 89081 Ulm, Germany

Abstract

CIDEM-501 is a hybrid antimicrobial peptide rationally designed based on the structure of panusin and panulirin template peptides. The new peptide exhibits significant antibacterial activity against multidrug-resistant pathogens (MIC = 2–4 μM) while conserving no toxicity in human cell lines. We conducted molecular dynamics (MD) simulations using the CHARMM-36 force field to explore the CIDEM-501 adsorption mechanism with different membrane compositions. Several parameters that characterize these interactions were analyzed to elucidate individual residues’ structural and thermodynamic contributions. The membrane models were constructed using CHARMM-GUI, mimicking the bacterial and eukaryotic phospholipid compositions. Molecular dynamics simulations were conducted over 500 ns, showing rapid and highly stable peptide adsorption to bacterial lipids components rather than the zwitterionic eucaryotic model membrane. A predominant peptide orientation was observed in all models dominated by an electric dipole. The peptide remained parallel to the membrane surface with the center loop oriented to the lipids. Our findings shed light on the antibacterial activity of CIDEM-501 on bacterial membranes and yield insights valuable for designing potent antimicrobial peptides targeting multi- and extreme drug-resistant bacteria.

Funder

CITMA Cuban Ministry of Science, Technology, and Environment

German Research Society

Alexander von Humboldt-Stiftung, Research Group Linkage Program

DAAD (Bonn, Germany) with funds from the German Federal Foreign Ministry

Publisher

MDPI AG

Reference79 articles.

1. Interagency Coordination Group on Antimicrobial Resistance (2023, August 03). No Time to Wait: Securing the Future from Drug-Resistant Infections. Report to the Secretary-General of the United Nations. Available online: https://www.Who.Int/Antimicrobial-Resistance/Interagency-Coordination-Group/Final-Report/En/.

2. Aljeldah, M.M. (2022). Antimicrobial Resistance and Its Spread Is a Global Threat. Antibiotics, 11.

3. COVID-19 and Antimicrobial Resistance: A Cross-Study;Rizvi;Sci. Total Environ.,2022

4. Chapter Ten The Structure/Function Relationship in Antimicrobial Peptides: What Can We Obtain from Structural Data?;Donev;Advances in Protein Chemistry and Structural Biology,2018

5. Ramazi, S., Mohammadi, N., Allahverdi, A., Khalili, E., and Abdolmaleki, P. (2022). A Review on Antimicrobial Peptides Databases and the Computational Tools. Database J. Biol. Databases Curation, 2022.

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