Machine Learning Models for Predicting Monoclonal Antibody Biophysical Properties from Molecular Dynamics Simulations and Deep Learning-Based Surface Descriptors

Monoclonal antibodies (mAbs) have found extensive applications and development in treating various diseases. From the pharmaceutical industry’s perspective, the journey from the design and development of mAbs to clinical testing and large-scale production is a highly time-consuming and resource-intensive process. During the research and development phase, assessing and optimizing the developability of mAbs is of paramount importance to ensure their success as candidates for therapeutic drugs. The critical factors influencing mAb development are their biophysical properties, such as aggregation propensity, solubility, and viscosity. This study utilized a data set comprising 12 biophysical properties of 137 antibodies from a previous study (Proc Natl Acad Sci USA. 114(5):944-949, 2017). We employed full-length antibody molecular dynamics simulations and machine learning techniques to predict experimental data for these 12 biophysical properties. Additionally, we utilized a newly developed deep learning model called DeepSP, which directly predicts the dynamical and structural properties of spatial aggregation propensity and spatial charge map in different antibody regions from sequences. Our research findings indicate that the machine learning models we developed outperform previous methods in predicting most biophysical properties. Furthermore, the DeepSP model yields similar predictive results compared to molecular dynamic simulations while significantly reducing computational time. The code and parameters are freely available at https://github.com/Lailabcode/AbDev. Also, the webapp, AbDev, for 12 biophysical properties prediction has been developed and provided at https://devpred.onrender.com/AbDev.