MolCRAFT: Structure-Based Drug Design in Continuous Parameter Space

Generative models for structure-based drug design (SBDD) have shown promising results in recent years. Existing works mainly focus on how to generate molecules with higher binding affinity, ignoring the feasibility prerequisites for generated 3D poses and resulting in false positives. We conduct thorough studies on key factors of ill-conformational problems when applying autoregressive methods and diffusion to SBDD, including mode collapse and hybrid continuous-discrete space. In this paper, we introduce \ours, the first SBDD model that operates in the continuous parameter space, together with a novel noise reduced sampling strategy. Empirical results show that our model consistently achieves superior performance in binding affinity with more stable 3D structure, demonstrating our ability to accurately model interatomic interactions. To our best knowledge, MolCRAFT is the first to achieve reference-level Vina Scores (-6.59 kcal/mol), outperforming other strong baselines by a wide margin (-0.84 kcal/mol). Code is available at https://github.com/AlgoMole/MolCRAFT.

Unified Generative Modeling of 3D Molecules via Bayesian Flow Networks

Advanced generative model (e.g., diffusion model) derived from simplified continuity assumptions of data distribution, though showing promising progress, has been difficult to apply directly to geometry generation applications due to the multi-modality and noise-sensitive nature of molecule geometry. This work introduces Geometric Bayesian Flow Networks (GeoBFN), which naturally fits molecule geometry by modeling diverse modalities in the differentiable parameter space of distributions. GeoBFN maintains the SE-(3) invariant density modeling property by incorporating equivariant inter-dependency modeling on parameters of distributions and unifying the probabilistic modeling of different modalities. Through optimized training and sampling techniques, we demonstrate that GeoBFN achieves state-of-the-art performance on multiple 3D molecule generation benchmarks in terms of generation quality (90.87% molecule stability in QM9 and 85.6% atom stability in GEOM-DRUG. GeoBFN can also conduct sampling with any number of steps to reach an optimal trade-off between efficiency and quality (e.g., 20-times speedup without sacrificing performance).

Equivariant Flow Matching with Hybrid Probability Transport

The generation of 3D molecules requires simultaneously deciding the categorical features~(atom types) and continuous features~(atom coordinates). Deep generative models, especially Diffusion Models (DMs), have demonstrated effectiveness in generating feature-rich geometries. However, existing DMs typically suffer from unstable probability dynamics with inefficient sampling speed. In this paper, we introduce geometric flow matching, which enjoys the advantages of both equivariant modeling and stabilized probability dynamics. More specifically, we propose a hybrid probability path where the coordinates probability path is regularized by an equivariant optimal transport, and the information between different modalities is aligned. Experimentally, the proposed method could consistently achieve better performance on multiple molecule generation benchmarks with 4.75$\times$ speed up of sampling on average.

Text Information Aggregation with Centrality Attention

A lot of natural language processing problems need to encode the text sequence as a fix-length vector, which usually involves aggregation process of combining the representations of all the words, such as pooling or self-attention. However, these widely used aggregation approaches did not take higher-order relationship among the words into consideration. Hence we propose a new way of obtaining aggregation weights, called eigen-centrality self-attention. More specifically, we build a fully-connected graph for all the words in a sentence, then compute the eigen-centrality as the attention score of each word. The explicit modeling of relationships as a graph is able to capture some higher-order dependency among words, which helps us achieve better results in 5 text classification tasks and one SNLI task than baseline models such as pooling, self-attention and dynamic routing. Besides, in order to compute the dominant eigenvector of the graph, we adopt power method algorithm to get the eigen-centrality measure. Moreover, we also derive an iterative approach to get the gradient for the power method process to reduce both memory consumption and computation requirement.}

Switch-LSTMs for Multi-Criteria Chinese Word Segmentation

Multi-criteria Chinese word segmentation is a promising but challenging task, which exploits several different segmentation criteria and mines their common underlying knowledge. In this paper, we propose a flexible multi-criteria learning for Chinese word segmentation. Usually, a segmentation criterion could be decomposed into multiple sub-criteria, which are shareable with other segmentation criteria. The process of word segmentation is a routing among these sub-criteria. From this perspective, we present Switch-LSTMs to segment words, which consist of several long short-term memory neural networks (LSTM), and a switcher to automatically switch the routing among these LSTMs. With these auto-switched LSTMs, our model provides a more flexible solution for multi-criteria CWS, which is also easy to transfer the learned knowledge to new criteria. Experiments show that our model obtains significant improvements on eight corpora with heterogeneous segmentation criteria, compared to the previous method and single-criterion learning.

Long Short-Term Memory with Dynamic Skip Connections

In recent years, long short-term memory (LSTM) has been successfully used to model sequential data of variable length. However, LSTM can still experience difficulty in capturing long-term dependencies. In this work, we tried to alleviate this problem by introducing a dynamic skip connection, which can learn to directly connect two dependent words. Since there is no dependency information in the training data, we propose a novel reinforcement learning-based method to model the dependency relationship and connect dependent words. The proposed model computes the recurrent transition functions based on the skip connections, which provides a dynamic skipping advantage over RNNs that always tackle entire sentences sequentially. Our experimental results on three natural language processing tasks demonstrate that the proposed method can achieve better performance than existing methods. In the number prediction experiment, the proposed model outperformed LSTM with respect to accuracy by nearly 20%.

Information Aggregation via Dynamic Routing for Sequence Encoding

While much progress has been made in how to encode a text sequence into a sequence of vectors, less attention has been paid to how to aggregate these preceding vectors (outputs of RNN/CNN) into fixed-size encoding vector. Usually, a simple max or average pooling is used, which is a bottom-up and passive way of aggregation and lack of guidance by task information. In this paper, we propose an aggregation mechanism to obtain a fixed-size encoding with a dynamic routing policy. The dynamic routing policy is dynamically deciding that what and how much information need be transferred from each word to the final encoding of the text sequence. Following the work of Capsule Network, we design two dynamic routing policies to aggregate the outputs of RNN/CNN encoding layer into a final encoding vector. Compared to the other aggregation methods, dynamic routing can refine the messages according to the state of final encoding vector. Experimental results on five text classification tasks show that our method outperforms other aggregating models by a significant margin. Related source code is released on our github page.

Overview of the NLPCC 2017 Shared Task: Chinese News Headline Categorization

In this paper, we give an overview for the shared task at the CCF Conference on Natural Language Processing \& Chinese Computing (NLPCC 2017): Chinese News Headline Categorization. The dataset of this shared task consists 18 classes, 12,000 short texts along with corresponded labels for each class. The dataset and example code can be accessed at https://github.com/FudanNLP/nlpcc2017_news_headline_categorization.

End-to-End Neural Sentence Ordering Using Pointer Network

Sentence ordering is one of important tasks in NLP. Previous works mainly focused on improving its performance by using pair-wise strategy. However, it is nontrivial for pair-wise models to incorporate the contextual sentence information. In addition, error prorogation could be introduced by using the pipeline strategy in pair-wise models. In this paper, we propose an end-to-end neural approach to address the sentence ordering problem, which uses the pointer network (Ptr-Net) to alleviate the error propagation problem and utilize the whole contextual information. Experimental results show the effectiveness of the proposed model. Source codes and dataset of this paper are available.