Machine Learning-Enabled Design and Prediction of Protein Resistance on Self-Assembled Monolayers and Beyond

The rational design of highly antifouling materials is crucial for a wide range of fundamental research and practical applications. The immense variety and complexity of the intrinsic physicochemical properties of materials (i.e., chemical structure, hydrophobicity, charge distribution, and molecular weight) and their surface coating properties (i.e., packing density, film thickness and roughness, and chain conformation) make it challenging to rationally design antifouling materials and reveal their fundamental structure-property relationships. In this work, we developed a data-driven machine learning model, a combination of factor analysis of functional group (FAFG), Pearson analysis, random forest (RF) and artificial neural network (ANN) algorithms, and Bayesian statistics, to computationally extract structure/chemical/surface features in correlation with the antifouling activity of self-assembled monolayers (SAMs) from a self-construction data set. The resultant model demonstrates the robustness of Q(CV)(2) = 0.90 and RMSECV = 0.21 and the predictive ability of Q(ext)(2) = 0.84 and RMSEext = 0.28, determines key descriptors and functional groups important for the antifouling activity, and enables to design original antifouling SAMs using the predicted antifouling functional groups. Three computationally designed molecules were further coated onto the surfaces in different forms of SAMs and polymer brushes. The resultant coatings with negative fouling indexes exhibited strong surface resistance to protein adsorption from undiluted blood serum and plasma, validating the model predictions. The data-driven machine learning model demonstrates their design and predictive capacity for next-generation antifouling materials and surfaces, which hopefully help to accelerate the discovery and understanding of functional materials.

Automated summary

A data-driven machine learning model was developed to computationally design highly antifouling self-assembled monolayers (SAMs), demonstrating robustness and predictive ability. Experimental validation confirmed the accuracy of the model predictions, showcasing its potential for accelerating the discovery and understanding of functional materials for next-generation antifouling surfaces.