Haotian Chu

Sirui Liu, Jun Zhang, Haotian Chu et al.

Proteins are essential component of human life and their structures are important for function and mechanism analysis. Recent work has shown the potential of AI-driven methods for protein structure prediction. However, the development of new models is restricted by the lack of dataset and benchmark training procedure. To the best of our knowledge, the existing open source datasets are far less to satisfy the needs of modern protein sequence-structure related research. To solve this problem, we present the first million-level protein structure prediction dataset with high coverage and diversity, named as PSP. This dataset consists of 570k true structure sequences (10TB) and 745k complementary distillation sequences (15TB). We provide in addition the benchmark training procedure for SOTA protein structure prediction model on this dataset. We validate the utility of this dataset for training by participating CAMEO contest in which our model won the first place. We hope our PSP dataset together with the training benchmark can enable a broader community of AI/biology researchers for AI-driven protein related research.

Jun Zhang, Sirui Liu, Mengyun Chen et al.

Data-driven predictive methods which can efficiently and accurately transform protein sequences into biologically active structures are highly valuable for scientific research and medical development. Determining accurate folding landscape using co-evolutionary information is fundamental to the success of modern protein structure prediction methods. As the state of the art, AlphaFold2 has dramatically raised the accuracy without performing explicit co-evolutionary analysis. Nevertheless, its performance still shows strong dependence on available sequence homologs. Based on the interrogation on the cause of such dependence, we presented EvoGen, a meta generative model, to remedy the underperformance of AlphaFold2 for poor MSA targets. By prompting the model with calibrated or virtually generated homologue sequences, EvoGen helps AlphaFold2 fold accurately in low-data regime and even achieve encouraging performance with single-sequence predictions. Being able to make accurate predictions with few-shot MSA not only generalizes AlphaFold2 better for orphan sequences, but also democratizes its use for high-throughput applications. Besides, EvoGen combined with AlphaFold2 yields a probabilistic structure generation method which could explore alternative conformations of protein sequences, and the task-aware differentiable algorithm for sequence generation will benefit other related tasks including protein design.

Xiang Huang, Zhanhong Ye, Hongsheng Liu et al.

Many important problems in science and engineering require solving the so-called parametric partial differential equations (PDEs), i.e., PDEs with different physical parameters, boundary conditions, shapes of computation domains, etc. Recently, building learning-based numerical solvers for parametric PDEs has become an emerging new field. One category of methods such as the Deep Galerkin Method (DGM) and Physics-Informed Neural Networks (PINNs) aim to approximate the solution of the PDEs. They are typically unsupervised and mesh-free, but require going through the time-consuming network training process from scratch for each set of parameters of the PDE. Another category of methods such as Fourier Neural Operator (FNO) and Deep Operator Network (DeepONet) try to approximate the solution mapping directly. Being fast with only one forward inference for each PDE parameter without retraining, they often require a large corpus of paired input-output observations drawn from numerical simulations, and most of them need a predefined mesh as well. In this paper, we propose Meta-Auto-Decoder (MAD), a mesh-free and unsupervised deep learning method that enables the pre-trained model to be quickly adapted to equation instances by implicitly encoding (possibly heterogenous) PDE parameters as latent vectors. The proposed method MAD can be interpreted by manifold learning in infinite-dimensional spaces, granting it a geometric insight. Extensive numerical experiments show that the MAD method exhibits faster convergence speed without losing accuracy than other deep learning-based methods. The project page with code is available: https://gitee.com/mindspore/mindscience/tree/master/MindElec/.

Xiang Huang, Hongsheng Liu, Beiji Shi et al.

In recent years, deep learning technology has been used to solve partial differential equations (PDEs), among which the physics-informed neural networks (PINNs) emerges to be a promising method for solving both forward and inverse PDE problems. PDEs with a point source that is expressed as a Dirac delta function in the governing equations are mathematical models of many physical processes. However, they cannot be solved directly by conventional PINNs method due to the singularity brought by the Dirac delta function. We propose a universal solution to tackle this problem with three novel techniques. Firstly the Dirac delta function is modeled as a continuous probability density function to eliminate the singularity; secondly a lower bound constrained uncertainty weighting algorithm is proposed to balance the PINNs losses between point source area and other areas; and thirdly a multi-scale deep neural network with periodic activation function is used to improve the accuracy and convergence speed of the PINNs method. We evaluate the proposed method with three representative PDEs, and the experimental results show that our method outperforms existing deep learning-based methods with respect to the accuracy, the efficiency and the versatility.