AMPCliff: quantitative definition and benchmarking of activity cliffs in antimicrobial peptides

Activity cliff (AC) is a phenomenon that a pair of similar molecules differ by a small structural alternation but exhibit a large difference in their biochemical activities. The AC of small molecules has been extensively investigated but limited knowledge is accumulated about the AC phenomenon in peptides with canonical amino acids. This study introduces a quantitative definition and benchmarking framework AMPCliff for the AC phenomenon in antimicrobial peptides (AMPs) composed by canonical amino acids. A comprehensive analysis of the existing AMP dataset reveals a significant prevalence of AC within AMPs. AMPCliff quantifies the activities of AMPs by the metric minimum inhibitory concentration (MIC), and defines 0.9 as the minimum threshold for the normalized BLOSUM62 similarity score between a pair of aligned peptides with at least two-fold MIC changes. This study establishes a benchmark dataset of paired AMPs in Staphylococcus aureus from the publicly available AMP dataset GRAMPA, and conducts a rigorous procedure to evaluate various AMP AC prediction models, including nine machine learning, four deep learning algorithms, four masked language models, and four generative language models. Our analysis reveals that these models are capable of detecting AMP AC events and the pre-trained protein language ESM2 model demonstrates superior performance across the evaluations. The predictive performance of AMP activity cliffs remains to be further improved, considering that ESM2 with 33 layers only achieves the Spearman correlation coefficient=0.50 for the regression task of the MIC values on the benchmark dataset. Source code and additional resources are available at https://www.healthinformaticslab.org/supp/ or https://github.com/Kewei2023/AMPCliff-generation.

PepHarmony: A Multi-View Contrastive Learning Framework for Integrated Sequence and Structure-Based Peptide Encoding

Recent advances in protein language models have catalyzed significant progress in peptide sequence representation. Despite extensive exploration in this field, pre-trained models tailored for peptide-specific needs remain largely unaddressed due to the difficulty in capturing the complex and sometimes unstable structures of peptides. This study introduces a novel multi-view contrastive learning framework PepHarmony for the sequence-based peptide encoding task. PepHarmony innovatively combines both sequence- and structure-level information into a sequence-level encoding module through contrastive learning. We carefully select datasets from the Protein Data Bank (PDB) and AlphaFold database to encompass a broad spectrum of peptide sequences and structures. The experimental data highlights PepHarmony's exceptional capability in capturing the intricate relationship between peptide sequences and structures compared with the baseline and fine-tuned models. The robustness of our model is confirmed through extensive ablation studies, which emphasize the crucial roles of contrastive loss and strategic data sorting in enhancing predictive performance. The proposed PepHarmony framework serves as a notable contribution to peptide representations, and offers valuable insights for future applications in peptide drug discovery and peptide engineering. We have made all the source code utilized in this study publicly accessible via GitHub at https://github.com/zhangruochi/PepHarmony or http://www.healthinformaticslab.org/supp/.

PepLand: a large-scale pre-trained peptide representation model for a comprehensive landscape of both canonical and non-canonical amino acids

In recent years, the scientific community has become increasingly interested on peptides with non-canonical amino acids due to their superior stability and resistance to proteolytic degradation. These peptides present promising modifications to biological, pharmacological, and physiochemical attributes in both endogenous and engineered peptides. Notwithstanding their considerable advantages, the scientific community exhibits a conspicuous absence of an effective pre-trained model adept at distilling feature representations from such complex peptide sequences. We herein propose PepLand, a novel pre-training architecture for representation and property analysis of peptides spanning both canonical and non-canonical amino acids. In essence, PepLand leverages a comprehensive multi-view heterogeneous graph neural network tailored to unveil the subtle structural representations of peptides. Empirical validations underscore PepLand's effectiveness across an array of peptide property predictions, encompassing protein-protein interactions, permeability, solubility, and synthesizability. The rigorous evaluation confirms PepLand's unparalleled capability in capturing salient synthetic peptide features, thereby laying a robust foundation for transformative advances in peptide-centric research domains. We have made all the source code utilized in this study publicly accessible via GitHub at https://github.com/zhangruochi/pepland

An FEA surrogate model with Boundary Oriented Graph Embedding approach

In this work, we present a Boundary Oriented Graph Embedding (BOGE) approach for the Graph Neural Network (GNN) to serve as a general surrogate model for regressing physical fields and solving boundary value problems. Providing shortcuts for both boundary elements and local neighbor elements, the BOGE approach can embed structured mesh elements into the graph and performs an efficient regression on large-scale triangular-mesh-based FEA results, which cannot be realized by other machine-learning-based surrogate methods. Focusing on the cantilever beam problem, our BOGE approach cannot only fit the distribution of stress fields but also regresses the topological optimization results, which show its potential of realizing abstract decision-making design process. The BOGE approach with 3-layer DeepGCN model \textcolor{blue}{achieves the regression with MSE of 0.011706 (2.41\% MAPE) for stress field prediction and 0.002735 MSE (with 1.58\% elements having error larger than 0.01) for topological optimization.} The overall concept of the BOGE approach paves the way for a general and efficient deep-learning-based FEA simulator that will benefit both industry and design-related areas.

Heuristic Black-box Adversarial Attacks on Video Recognition Models

We study the problem of attacking video recognition models in the black-box setting, where the model information is unknown and the adversary can only make queries to detect the predicted top-1 class and its probability. Compared with the black-box attack on images, attacking videos is more challenging as the computation cost for searching the adversarial perturbations on a video is much higher due to its high dimensionality. To overcome this challenge, we propose a heuristic black-box attack model that generates adversarial perturbations only on the selected frames and regions. More specifically, a heuristic-based algorithm is proposed to measure the importance of each frame in the video towards generating the adversarial examples. Based on the frames' importance, the proposed algorithm heuristically searches a subset of frames where the generated adversarial example has strong adversarial attack ability while keeps the perturbations lower than the given bound. Besides, to further boost the attack efficiency, we propose to generate the perturbations only on the salient regions of the selected frames. In this way, the generated perturbations are sparse in both temporal and spatial domains. Experimental results of attacking two mainstream video recognition methods on the UCF-101 dataset and the HMDB-51 dataset demonstrate that the proposed heuristic black-box adversarial attack method can significantly reduce the computation cost and lead to more than 28\% reduction in query numbers for the untargeted attack on both datasets.