GPCR-BERT: Interpreting Sequential Design of G Protein Coupled Receptors Using Protein Language Models

With the rise of Transformers and Large Language Models (LLMs) in Chemistry and Biology, new avenues for the design and understanding of therapeutics have opened up to the scientific community. Protein sequences can be modeled as language and can take advantage of recent advances in LLMs, specifically with the abundance of our access to the protein sequence datasets. In this paper, we developed the GPCR-BERT model for understanding the sequential design of G Protein-Coupled Receptors (GPCRs). GPCRs are the target of over one-third of FDA-approved pharmaceuticals. However, there is a lack of comprehensive understanding regarding the relationship between amino acid sequence, ligand selectivity, and conformational motifs (such as NPxxY, CWxP, E/DRY). By utilizing the pre-trained protein model (Prot-Bert) and fine-tuning with prediction tasks of variations in the motifs, we were able to shed light on several relationships between residues in the binding pocket and some of the conserved motifs. To achieve this, we took advantage of attention weights, and hidden states of the model that are interpreted to extract the extent of contributions of amino acids in dictating the type of masked ones. The fine-tuned models demonstrated high accuracy in predicting hidden residues within the motifs. In addition, the analysis of embedding was performed over 3D structures to elucidate the higher-order interactions within the conformations of the receptors.

PeptideBERT: A Language Model based on Transformers for Peptide Property Prediction

Recent advances in Language Models have enabled the protein modeling community with a powerful tool since protein sequences can be represented as text. Specifically, by taking advantage of Transformers, sequence-to-property prediction will be amenable without the need for explicit structural data. In this work, inspired by recent progress in Large Language Models (LLMs), we introduce PeptideBERT, a protein language model for predicting three key properties of peptides (hemolysis, solubility, and non-fouling). The PeptideBert utilizes the ProtBERT pretrained transformer model with 12 attention heads and 12 hidden layers. We then finetuned the pretrained model for the three downstream tasks. Our model has achieved state of the art (SOTA) for predicting Hemolysis, which is a task for determining peptide's potential to induce red blood cell lysis. Our PeptideBert non-fouling model also achieved remarkable accuracy in predicting peptide's capacity to resist non-specific interactions. This model, trained predominantly on shorter sequences, benefits from the dataset where negative examples are largely associated with insoluble peptides. Codes, models, and data used in this study are freely available at: https://github.com/ChakradharG/PeptideBERT

UpCycling: Semi-supervised 3D Object Detection without Sharing Raw-level Unlabeled Scenes

Semi-supervised Learning (SSL) has received increasing attention in autonomous driving to relieve enormous burden for 3D annotation. In this paper, we propose UpCycling, a novel SSL framework for 3D object detection with zero additional raw-level point cloud: learning from unlabeled de-identified intermediate features (i.e., smashed data) for privacy preservation. The intermediate features do not require additional computation on autonomous vehicles since they are naturally produced by the inference pipeline. However, augmenting 3D scenes at a feature level turns out to be a critical issue: applying the augmentation methods in the latest semi-supervised 3D object detectors distorts intermediate features, which causes the pseudo-labels to suffer from significant noise. To solve the distortion problem while achieving highly effective SSL, we introduce hybrid pseudo labels, feature-level Ground Truth sampling (F-GT) and Rotation (F-RoT), which safely augment unlabeled multi-type 3D scene features and provide high-quality supervision. We implement UpCycling on two representative 3D object detection models, SECOND-IoU and PV-RCNN, and perform experiments on widely-used datasets (Waymo, KITTI, and Lyft). While preserving privacy with zero raw-point scene, UpCycling significantly outperforms the state-of-the-art SSL methods that utilize raw-point scenes, in both domain adaptation and partial-label scenarios.