Computational and Structural Biotechnology Journal (Dec 2024)
DeepSP: Deep learning-based spatial properties to predict monoclonal antibody stability
Abstract
Therapeutic antibody development faces challenges due to high viscosities and aggregation tendencies. The spatial charge map (SCM) and spatial aggregation propensity (SAP) are computational techniques that aid in predicting viscosity and aggregation, respectively. These methods rely on structural data derived from molecular dynamics (MD) simulations, which are computationally demanding. DeepSCM, a deep learning surrogate model based on sequence information to predict SCM, was recently developed to screen high-concentration antibody viscosity. This study further utilized a dataset of 20,530 antibody sequences to train a convolutional neural network deep learning surrogate model called Deep Spatial Properties (DeepSP). DeepSP directly predicts SAP and SCM scores in different domains of antibody variable regions based solely on their sequences without performing MD simulations. The linear correlation coefficient between DeepSP scores and MD-derived scores for 30 properties achieved values between 0.76 and 0.96 with an average of 0.87. DeepSP descriptors were employed as features to build machine learning models to predict the aggregation rate of 21 antibodies, and the performance is similar to the results obtained from the previous study using MD simulations. This result demonstrates that the DeepSP approach significantly reduces the computational time required compared to MD simulations. The DeepSP model enables the rapid generation of 30 structural properties that can also be used as features in other research to train machine learning models for predicting various antibody stability using sequences only. DeepSP is freely available as an online tool via https://deepspwebapp.onrender.com and the codes and parameters are freely available at https://github.com/Lailabcode/DeepSP.
