Developing Differentiable Long-Range Force Field for Proteins with E(3) Neural Network Predicted Asymptotic Parameters

Accurately describing long-range interactions is a significant challenge in molecular dynamics (MD) simulations of proteins. And high-quality long-range potential is also an important component of range-separated machine learning force field. This study introduces a comprehensive asymptotic parameter database, encompassing atomic multipole moments, polarizabilities, and dispersion coefficients. Leveraging active learning, our database comprehensively represents protein fragments with up to 8 heavy atoms, capturing their conformational diversity with merely 78,000 data points. Additionally, E(3) neural network (E3NN) is employed to predict the asymptotic parameters directly from the local geometry. The E3NN models demonstrate exceptional accuracy and transferability across all asymptotic parameters, achieving an R2 of 0.999 for both protein fragments and 20 amino acid dipeptide test sets. The long range electrostatic and dispersion energies can be obtained using the the E3NN-predited parameters, with an error of 0.07 and 0.02 kcal/mol, respectively, when compared to Symmetry-Adapted Perturbation Theory (SAPT). Therefore, our force fields demonstrate the capability to accurately describe long-range interactions in proteins, paving the way for the nextgeneration protein force fields.