Molecular Dynamics Simulations Cyclotide Kalata B1 Interactions with Lipid Bilayers
Neville Y Forlemu1, Eric N Njabon2, Ajay Mallia1
1School of Science and Technology, Chemistry Program, Georgia Gwinnett College, 1000 University Center Lane, Lawrenceville, GA 30043, USA.
Molecules (Basel, Switzerland)
|April 14, 2026
Summary
Cyclotides like kalata B1 interact with lipid membranes via surface association, not deep insertion. Their stable structure remains intact, with interactions depending on lipid headgroups, influencing peptide orientation and membrane dynamics.
Area of Science:
- Biophysics
- Molecular Biology
- Computational Chemistry
Background:
- Cyclotides are stable plant peptides with membrane-interacting biological activities.
- The precise molecular mechanisms of cyclotide-lipid membrane interactions are not fully understood.
Purpose of the Study:
- To investigate the membrane association of the cyclotide kalata B1 with different phospholipid bilayers using molecular dynamics simulations.
- To elucidate the molecular mechanisms and lipid selectivity governing cyclotide-membrane interactions.
Main Methods:
- Microsecond-scale (1 μs) all-atom molecular dynamics simulations.
- Investigated kalata B1 interaction with POPC, POPE, and POPG phospholipid bilayers.
- Analyzed peptide orientation, conformational flexibility, and lipid response.
Main Results:
- Kalata B1 rapidly adsorbs to membrane surfaces, maintaining structural integrity.
- Lipid headgroup composition influences peptide orientation and dynamics, not deep insertion.
- POPC favors upright configurations; POPE and POPG promote lateral spreading.
- Membrane perturbations are localized to the peptide-exposed leaflet.
Conclusions:
- Cyclotide membrane activity is governed by interfacial, headgroup-dependent mechanisms.
- Results reconcile experimental data and provide molecular insights into cyclotide-lipid interactions.
- Findings can inform the design of novel cyclotide-based bioactive agents.
