Do Deep Learning Methods Really Perform Better in Molecular Conformation Generation?

Molecular conformation generation (MCG) is a fundamental and important problem in drug discovery. Many traditional methods have been developed to solve the MCG problem, such as systematic searching, model-building, random searching, distance geometry, molecular dynamics, Monte Carlo methods, etc. However, they have some limitations depending on the molecular structures. Recently, there are plenty of deep learning based MCG methods, which claim they largely outperform the traditional methods. However, to our surprise, we design a simple and cheap algorithm (parameter-free) based on the traditional methods and find it is comparable to or even outperforms deep learning based MCG methods in the widely used GEOM-QM9 and GEOM-Drugs benchmarks. In particular, our design algorithm is simply the clustering of the RDKIT-generated conformations. We hope our findings can help the community to revise the deep learning methods for MCG. The code of the proposed algorithm could be found at https://gist.github.com/ZhouGengmo/5b565f51adafcd911c0bc115b2ef027c

3D Molecular Generation via Virtual Dynamics

Structure-based drug design, i.e., finding molecules with high affinities to the target protein pocket, is one of the most critical tasks in drug discovery. Traditional solutions, like virtual screening, require exhaustively searching on a large molecular database, which are inefficient and cannot return novel molecules beyond the database. The pocket-based 3D molecular generation model, i.e., directly generating a molecule with a 3D structure and binding position in the pocket, is a new promising way to address this issue. Herein, we propose VD-Gen, a novel pocket-based 3D molecular generation pipeline. VD-Gen consists of several carefully designed stages to generate fine-grained 3D molecules with binding positions in the pocket cavity end-to-end. Rather than directly generating or sampling atoms with 3D positions in the pocket like in early attempts, in VD-Gen, we first randomly initialize many virtual particles in the pocket; then iteratively move these virtual particles, making the distribution of virtual particles approximate the distribution of molecular atoms. After virtual particles are stabilized in 3D space, we extract a 3D molecule from them. Finally, we further refine atoms in the extracted molecule by iterative movement again, to get a high-quality 3D molecule, and predict a confidence score for it. Extensive experiment results on pocket-based molecular generation demonstrate that VD-Gen can generate novel 3D molecules to fill the target pocket cavity with high binding affinities, significantly outperforming previous baselines

Adversarial Meta Sampling for Multilingual Low-Resource Speech Recognition

Low-resource automatic speech recognition (ASR) is challenging, as the low-resource target language data cannot well train an ASR model. To solve this issue, meta-learning formulates ASR for each source language into many small ASR tasks and meta-learns a model initialization on all tasks from different source languages to access fast adaptation on unseen target languages. However, for different source languages, the quantity and difficulty vary greatly because of their different data scales and diverse phonological systems, which leads to task-quantity and task-difficulty imbalance issues and thus a failure of multilingual meta-learning ASR (MML-ASR). In this work, we solve this problem by developing a novel adversarial meta sampling (AMS) approach to improve MML-ASR. When sampling tasks in MML-ASR, AMS adaptively determines the task sampling probability for each source language. Specifically, for each source language, if the query loss is large, it means that its tasks are not well sampled to train ASR model in terms of its quantity and difficulty and thus should be sampled more frequently for extra learning. Inspired by this fact, we feed the historical task query loss of all source language domain into a network to learn a task sampling policy for adversarially increasing the current query loss of MML-ASR. Thus, the learnt task sampling policy can master the learning situation of each language and thus predicts good task sampling probability for each language for more effective learning. Finally, experiment results on two multilingual datasets show significant performance improvement when applying our AMS on MML-ASR, and also demonstrate the applicability of AMS to other low-resource speech tasks and transfer learning ASR approaches.Comment: accepted in AAAI202

Uni-QSAR: an Auto-ML Tool for Molecular Property Prediction

Recently deep learning based quantitative structure-activity relationship (QSAR) models has shown surpassing performance than traditional methods for property prediction tasks in drug discovery. However, most DL based QSAR models are restricted to limited labeled data to achieve better performance, and also are sensitive to model scale and hyper-parameters. In this paper, we propose Uni-QSAR, a powerful Auto-ML tool for molecule property prediction tasks. Uni-QSAR combines molecular representation learning (MRL) of 1D sequential tokens, 2D topology graphs, and 3D conformers with pretraining models to leverage rich representation from large-scale unlabeled data. Without any manual fine-tuning or model selection, Uni-QSAR outperforms SOTA in 21/22 tasks of the Therapeutic Data Commons (TDC) benchmark under designed parallel workflow, with an average performance improvement of 6.09\%. Furthermore, we demonstrate the practical usefulness of Uni-QSAR in drug discovery domains