Decomposed Direct Preference Optimization for Structure-Based Drug Design

Diffusion models have achieved promising results for Structure-Based Drug Design (SBDD). Nevertheless, high-quality protein subpocket and ligand data are relatively scarce, which hinders the models' generation capabilities. Recently, Direct Preference Optimization (DPO) has emerged as a pivotal tool for the alignment of generative models such as large language models and diffusion models, providing greater flexibility and accuracy by directly aligning model outputs with human preferences. Building on this advancement, we introduce DPO to SBDD in this paper. We tailor diffusion models to pharmaceutical needs by aligning them with elaborately designed chemical score functions. We propose a new structure-based molecular optimization method called DecompDPO, which decomposes the molecule into arms and scaffolds and performs preference optimization at both local substructure and global molecule levels, allowing for more precise control with fine-grained preferences. Notably, DecompDPO can be effectively used for two main purposes: (1) fine-tuning pretrained diffusion models for molecule generation across various protein families, and (2) molecular optimization given a specific protein subpocket after generation. Extensive experiments on the CrossDocked2020 benchmark show that DecompDPO significantly improves model performance in both molecule generation and optimization, with up to 100% Median High Affinity and a 54.9% Success Rate.

Implicit Multi-Spectral Transformer: An Lightweight and Effective Visible to Infrared Image Translation Model

In the field of computer vision, visible light images often exhibit low contrast in low-light conditions, presenting a significant challenge. While infrared imagery provides a potential solution, its utilization entails high costs and practical limitations. Recent advancements in deep learning, particularly the deployment of Generative Adversarial Networks (GANs), have facilitated the transformation of visible light images to infrared images. However, these methods often experience unstable training phases and may produce suboptimal outputs. To address these issues, we propose a novel end-to-end Transformer-based model that efficiently converts visible light images into high-fidelity infrared images. Initially, the Texture Mapping Module and Color Perception Adapter collaborate to extract texture and color features from the visible light image. The Dynamic Fusion Aggregation Module subsequently integrates these features. Finally, the transformation into an infrared image is refined through the synergistic action of the Color Perception Adapter and the Enhanced Perception Attention mechanism. Comprehensive benchmarking experiments confirm that our model outperforms existing methods, producing infrared images of markedly superior quality, both qualitatively and quantitatively. Furthermore, the proposed model enables more effective downstream applications for infrared images than other methods.

Antigen-Specific Antibody Design via Direct Energy-based Preference Optimization

Antibody design, a crucial task with significant implications across various disciplines such as therapeutics and biology, presents considerable challenges due to its intricate nature. In this paper, we tackle antigen-specific antibody design as a protein sequence-structure co-design problem, considering both rationality and functionality. Leveraging a pre-trained conditional diffusion model that jointly models sequences and structures of complementarity-determining regions (CDR) in antibodies with equivariant neural networks, we propose direct energy-based preference optimization to guide the generation of antibodies with both rational structures and considerable binding affinities to given antigens. Our method involves fine-tuning the pre-trained diffusion model using a residue-level decomposed energy preference. Additionally, we employ gradient surgery to address conflicts between various types of energy, such as attraction and repulsion. Experiments on RAbD benchmark show that our approach effectively optimizes the energy of generated antibodies and achieves state-of-the-art performance in designing high-quality antibodies with low total energy and high binding affinity, demonstrating the superiority of our approach.

Stabilizing Policy Gradients for Stochastic Differential Equations via Consistency with Perturbation Process

Considering generating samples with high rewards, we focus on optimizing deep neural networks parameterized stochastic differential equations (SDEs), the advanced generative models with high expressiveness, with policy gradient, the leading algorithm in reinforcement learning. Nevertheless, when applying policy gradients to SDEs, since the policy gradient is estimated on a finite set of trajectories, it can be ill-defined, and the policy behavior in data-scarce regions may be uncontrolled. This challenge compromises the stability of policy gradients and negatively impacts sample complexity. To address these issues, we propose constraining the SDE to be consistent with its associated perturbation process. Since the perturbation process covers the entire space and is easy to sample, we can mitigate the aforementioned problems. Our framework offers a general approach allowing for a versatile selection of policy gradient methods to effectively and efficiently train SDEs. We evaluate our algorithm on the task of structure-based drug design and optimize the binding affinity of generated ligand molecules. Our method achieves the best Vina score -9.07 on the CrossDocked2020 dataset.

GSLB: The Graph Structure Learning Benchmark

Graph Structure Learning (GSL) has recently garnered considerable attention due to its ability to optimize both the parameters of Graph Neural Networks (GNNs) and the computation graph structure simultaneously. Despite the proliferation of GSL methods developed in recent years, there is no standard experimental setting or fair comparison for performance evaluation, which creates a great obstacle to understanding the progress in this field. To fill this gap, we systematically analyze the performance of GSL in different scenarios and develop a comprehensive Graph Structure Learning Benchmark (GSLB) curated from 20 diverse graph datasets and 16 distinct GSL algorithms. Specifically, GSLB systematically investigates the characteristics of GSL in terms of three dimensions: effectiveness, robustness, and complexity. We comprehensively evaluate state-of-the-art GSL algorithms in node- and graph-level tasks, and analyze their performance in robust learning and model complexity. Further, to facilitate reproducible research, we have developed an easy-to-use library for training, evaluating, and visualizing different GSL methods. Empirical results of our extensive experiments demonstrate the ability of GSL and reveal its potential benefits on various downstream tasks, offering insights and opportunities for future research. The code of GSLB is available at: https://github.com/GSL-Benchmark/GSLB.

Synthetic Data Are as Good as the Real for Association Knowledge Learning in Multi-object Tracking

Association, aiming to link bounding boxes of the same identity in a video sequence, is a central component in multi-object tracking (MOT). To train association modules, e.g., parametric networks, real video data are usually used. However, annotating person tracks in consecutive video frames is expensive, and such real data, due to its inflexibility, offer us limited opportunities to evaluate the system performance w.r.t changing tracking scenarios. In this paper, we study whether 3D synthetic data can replace real-world videos for association training. Specifically, we introduce a large-scale synthetic data engine named MOTX, where the motion characteristics of cameras and objects are manually configured to be similar to those in real-world datasets. We show that compared with real data, association knowledge obtained from synthetic data can achieve very similar performance on real-world test sets without domain adaption techniques. Our intriguing observation is credited to two factors. First and foremost, 3D engines can well simulate motion factors such as camera movement, camera view and object movement, so that the simulated videos can provide association modules with effective motion features. Second, experimental results show that the appearance domain gap hardly harms the learning of association knowledge. In addition, the strong customization ability of MOTX allows us to quantitatively assess the impact of motion factors on MOT, which brings new insights to the community.

Global Sparse Momentum SGD for Pruning Very Deep Neural Networks

Deep Neural Network (DNN) is powerful but computationally expensive and memory intensive, thus impeding its practical usage on resource-constrained front-end devices. DNN pruning is an approach for deep model compression, which aims at eliminating some parameters with tolerable performance degradation. In this paper, we propose a novel momentum-SGD-based optimization method to reduce the network complexity by on-the-fly pruning. Concretely, given a global compression ratio, we categorize all the parameters into two parts at each training iteration which are updated using different rules. In this way, we gradually zero out the redundant parameters, as we update them using only the ordinary weight decay but no gradients derived from the objective function. As a departure from prior methods that require heavy human works to tune the layer-wise sparsity ratios, prune by solving complicated non-differentiable problems or finetune the model after pruning, our method is characterized by 1) global compression that automatically finds the appropriate per-layer sparsity ratios; 2) end-to-end training; 3) no need for a time-consuming re-training process after pruning; and 4) superior capability to find better winning tickets which have won the initialization lottery.

Class-balanced Grouping and Sampling for Point Cloud 3D Object Detection

This report presents our method which wins the nuScenes3D Detection Challenge [17] held in Workshop on Autonomous Driving(WAD, CVPR 2019). Generally, we utilize sparse 3D convolution to extract rich semantic features, which are then fed into a class-balanced multi-head network to perform 3D object detection. To handle the severe class imbalance problem inherent in the autonomous driving scenarios, we design a class-balanced sampling and augmentation strategy to generate a more balanced data distribution. Furthermore, we propose a balanced group-ing head to boost the performance for the categories withsimilar shapes. Based on the Challenge results, our methodoutperforms the PointPillars [14] baseline by a large mar-gin across all metrics, achieving state-of-the-art detection performance on the nuScenes dataset. Code will be released at CBGS.