Statistical Survey of Chemical and Geometric Patterns on Protein Surfaces as a Blueprint for Protein-mimicking Nanoparticles

TL;DR

This study systematically analyzes protein surface features and compares them with functionalized nanoparticles, providing insights for designing synthetic nanoobjects that mimic protein surface properties for biomedical applications.

Contribution

It offers the first comprehensive statistical survey of protein surface patterns and their comparison with nanoparticle surfaces, guiding the rational design of protein-mimicking nanomaterials.

Findings

Protein surfaces exhibit characteristic charge and hydrophobic patches.

Nanoparticles show similar surface patch patterns to proteins.

Differences between protein and nanoparticle surface features are identified.

Abstract

Despite recent breakthroughs in understanding how protein sequence relates to structure and function, considerably less attention has been paid to the general features of protein surfaces beyond those regions involved in binding and catalysis. This paper provides a systematic survey of the universe of protein surfaces and quantifies the sizes, shapes, and curvatures of the positively/negatively charged and hydrophobic/hydrophilic surface patches as well as correlations between such patches. It then compares these statistics with the metrics characterizing nanoparticles functionalized with ligands terminated with positively and negatively charged ligands. These particles are of particular interest because they are also surface-patchy and have been shown to exhibit both antibiotic and anticancer activities - via selective interactions against various cellular structures - prompting loose analogies to proteins. Our analyses support such analogies in several respects (e.g., patterns of charged protrusions and hydrophobic niches similar to those observed in proteins), although there are also significant differences. Looking forward, this work provides a blueprint for the rational design of synthetic nanoobjects with further enhanced mimicry of proteins' surface properties.