Molecular dynamics simulation and conformational analysis of some catalytically active peptides

Area of Science:

• Peptide Science
• Computational Chemistry
• Biophysics

Background:

• Developing stable, inexpensive artificial enzymes with high catalytic activity is crucial in peptide science.
• Understanding factors influencing enzyme conformation and their link to catalytic activity is the primary design challenge.

Purpose of the Study:

• To investigate the conformational preferences of two catalytically active peptides (Fmoc-Phe-Phe-His-CONH2 and Fmoc-Phe-Phe-Arg-CONH2) using molecular dynamics simulations.
• To correlate observed peptide conformations with temperature variations and water-peptide interactions.

Main Methods:

• Molecular dynamics (MD) simulations in explicit water at 300, 400, and 500 K.
• Conformational analysis using Ramachandran plots and radius of gyration (Rg).
• Radial distribution functions (RDF) to analyze water-peptide interactions.

Main Results:

• Both peptides exhibited conformational flexibility and a preference for helical structures.
• Increased temperature led to decreased side-chain contacts in both peptides.
• Peptide 2 (with Arginine) showed stronger water-peptide interactions around its nitrogen atoms compared to Peptide 1 (with Histidine).

Conclusions:

• Differences in secondary structures between the two peptides are attributed to distinct water molecule arrangements around Arginine and Histidine residues.
• These findings offer insights into peptide conformations crucial for designing novel peptide analogs and artificial enzymes.