Refining Peptide Design for Surface Binding

Solid-binding peptides (SBPs) are short amino acid sequences that can selectively bind to organic or inorganic surfaces, enabling scientists to modify surface compositions without using harsh chemicals. This feature has made SBPs invaluable to biosensing, which require such precision to accurately bind detected molecules. Pushpavanam et al. developed a computational technique that allows scientists to discover new SBPs with improved precision over traditional methods.

The study addressed issues found with existing discovery techniques, which encounter biases and constraints that tend to result in the exclusion of SBPs with high binding affinities.

“Binding affinity is strongly influenced by a peptide’s sequence and structural flexibility,” said author Karthik Pushpavanam. “To improve binding, avoid clustering charged or bulky residues, which cause repulsion and steric clashes; rigid secondary structures, which limit flexibility; consecutive aliphatic residues, which form non-interactive zones; and consecutive prolines, which induce stiffness and reduce contact formation.”

The key discovery was using molecular dynamics simulations, which allowed the scientists to compare 46 peptides under identical conditions and eliminate selection bias.

The authors chose and simulated the 46 peptides using a molecular dynamics tool that modeled the peptides binding to a gold surface solvated with water. Three independent simulations were conducted for each peptide to ensure statistical validity. Afterwards, the authors calculated the interaction energies and distances between molecules and recreated a structural model of the peptide bonding.

For future work, the authors will modify their technique to accommodate peptides with charges on their surface, to examine how these charges influence binding behavior.

Source: “Promiscuous binding peptides - Computational screening reveals higher-affinity peptides for gold binding beyond phage display selections,” by M. Aditya, P. Adwaith, A. Krishna, K. S. Reman, and K. Pushpavanam, Biointerphases (2025). The article can be accessed at https://doi.org/10.1116/6.0004790 .

This paper is part of the Biointerfaces in India Collection, learn more here .