In drug discovery, molecular dynamics (MD) simulation for protein-ligand binding provides a powerful tool for predicting binding affinities, estimating transport properties, and exploring pocket sites. There has been a long history of improving the efficiency of MD simulations through better numerical methods and, more recently, by utilizing machine learning (ML) methods. Yet, challenges remain, such as accurate modeling of extended-timescale simulations. To address this issue, we propose NeuralMD, the first ML surrogate that can facilitate numerical MD and provide accurate simulations in protein-ligand binding. We propose a principled approach that incorporates a novel physics-informed multi-grained group symmetric framework. Specifically, we propose (1) a BindingNet model that satisfies group symmetry using vector frames and captures the multi-level protein-ligand interactions, and (2) an augmented neural differential equation solver that learns the trajectory under Newtonian mechanics. For the experiment, we design ten single-trajectory and three multi-trajectory binding simulation tasks. We show the efficiency and effectiveness of NeuralMD, with a 2000$\times$ speedup over standard numerical MD simulation and outperforming all other ML approaches by up to 80% under the stability metric. We further qualitatively show that NeuralMD reaches more stable binding predictions compared to other machine learning methods.

Modeling the complex three-dimensional (3D) dynamics of relational systems is an important problem in the natural sciences, with applications ranging from molecular simulations to particle mechanics. Machine learning methods have achieved good success by learning graph neural networks to model spatial interactions. However, these approaches do not faithfully capture temporal correlations since they only model next-step predictions. In this work, we propose Equivariant Graph Neural Operator (EGNO), a novel and principled method that directly models dynamics as trajectories instead of just next-step prediction. Different from existing methods, EGNO explicitly learns the temporal evolution of 3D dynamics where we formulate the dynamics as a function over time and learn neural operators to approximate it. To capture the temporal correlations while keeping the intrinsic SE(3)-equivariance, we develop equivariant temporal convolutions parameterized in the Fourier space and build EGNO by stacking the Fourier layers over equivariant networks. EGNO is the first operator learning framework that is capable of modeling solution dynamics functions over time while retaining 3D equivariance. Comprehensive experiments in multiple domains, including particle simulations, human motion capture, and molecular dynamics, demonstrate the significantly superior performance of EGNO against existing methods, thanks to the equivariant temporal modeling.

Scientific discovery and engineering design are currently limited by the time and cost of physical experiments, selected mostly through trial-and-error and intuition that require deep domain expertise. Numerical simulations present an alternative to physical experiments but are usually infeasible for complex real-world domains due to the computational requirements of existing numerical methods. Artificial intelligence (AI) presents a potential paradigm shift by developing fast data-driven surrogate models. In particular, an AI framework, known as Neural Operators, presents a principled framework for learning mappings between functions defined on continuous domains, e.g., spatiotemporal processes and partial differential equations (PDE). They can extrapolate and predict solutions at new locations unseen during training, i.e., perform zero-shot super-resolution. Neural Operators can augment or even replace existing simulators in many applications, such as computational fluid dynamics, weather forecasting, and material modeling, while being 4-5 orders of magnitude faster. Further, Neural Operators can be integrated with physics and other domain constraints enforced at finer resolutions to obtain high-fidelity solutions and good generalization. Since Neural Operators are differentiable, they can directly optimize parameters for inverse design and other inverse problems. We believe that Neural Operators present a transformative approach to simulation and design, enabling rapid research and development.

The theory of greedy low-rank learning (GLRL) aims to explain the impressive generalization capabilities of deep learning. It proves that stochastic gradient-based training implicitly regularizes neural networks towards low-rank solutions through a gradual increase of the rank during training. However, there is a gap between theory and practice since GLRL requires an infinitesimal initialization of the weights, which is not practical due to the fact that it is a saddle point. In this work, we remove the assumption of infinitesimal initialization by focusing on cumulative weight updates. We prove the cumulative weight updates follow an incremental low-rank trajectory for arbitrary orthogonal initialization of weights in a three-layer linear network. Empirically, we demonstrate that our theory holds on a broad range of neural networks (e.g., transformers) and standard training algorithms (e.g., SGD, Adam). However, existing training algorithms do not exploit the low-rank property to improve computational efficiency as the networks are not parameterized in low-rank. To remedy this, we design a new training algorithm Incremental Low-Rank Learning (InRank), which explicitly expresses cumulative weight updates as low-rank matrices while incrementally augmenting their ranks during training. We evaluate InRank on GPT-2, and our results indicate that InRank achieves comparable prediction performance as the full-rank counterpart while requiring at most 33% of the total ranks throughout training. We also propose an efficient version of InRank that achieves a reduction of 37% in total training time and 36% in model size when training GPT-medium on WikiText-103 from scratch.

Large decoder-only language models (LMs) can be largely improved in terms of perplexity by retrieval (e.g., RETRO), but its impact on text generation quality and downstream task accuracy is unclear. Thus, it is still an open question: shall we pretrain large autoregressive LMs with retrieval? To answer it, we perform a comprehensive study on a scalable pre-trained retrieval-augmented LM (i.e., RETRO) compared with standard GPT and retrieval-augmented GPT incorporated at fine-tuning or inference stages. We first provide the recipe to reproduce RETRO up to 9.5B parameters while retrieving a text corpus with 330B tokens. Based on that, we have the following novel findings: i) RETRO outperforms GPT on text generation with much less degeneration (i.e., repetition), moderately higher factual accuracy, and slightly lower toxicity with a nontoxic retrieval database. ii) On the LM Evaluation Harness benchmark, RETRO largely outperforms GPT on knowledge-intensive tasks, but is on par with GPT on other tasks. Furthermore, we introduce a simple variant of the model, RETRO++, which largely improves open-domain QA results of original RETRO (e.g., EM score +8.6 on Natural Question) and significantly outperforms retrieval-augmented GPT in both fine-tuning and zero-shot evaluation settings. Our findings highlight the promising direction of pretraining autoregressive LMs with retrieval as future foundation models. We release our code and model at: https://github.com/NVIDIA/Megatron-LM/blob/main/tools/retro/README.md

The goal of this series is to chronicle opinions and issues in the field of machine learning as they stand today and as they change over time. The plan is to host this survey periodically until the AI singularity paperclip-frenzy-driven doomsday, keeping an updated list of topical questions and interviewing new community members for each edition.

Pretrained Language Models (PLMs) harbor inherent social biases that can result in harmful real-world implications. Such social biases are measured through the probability values that PLMs output for different social groups and attributes appearing in a set of test sentences. However, bias testing is currently cumbersome since the test sentences are generated either from a limited set of manual templates or need expensive crowd-sourcing. We instead propose using ChatGPT for the controllable generation of test sentences, given any arbitrary user-specified combination of social groups and attributes appearing in the test sentences. When compared to template-based methods, our approach using ChatGPT for test sentence generation is superior in detecting social bias, especially in challenging settings such as intersectional biases. We present an open-source comprehensive bias testing framework (BiasTestGPT), hosted on HuggingFace, that can be plugged into any open-source PLM for bias testing. User testing with domain experts from various fields has shown their interest in being able to test modern AI for social biases. Our tool has significantly improved their awareness of such biases in PLMs, proving to be learnable and user-friendly. We thus enable seamless open-ended social bias testing of PLMs by domain experts through an automatic large-scale generation of diverse test sentences for any combination of social categories and attributes.

Quantification of real-time informal feedback delivered by an experienced surgeon to a trainee during surgery is important for skill improvements in surgical training. Such feedback in the live operating room is inherently multimodal, consisting of verbal conversations (e.g., questions and answers) as well as non-verbal elements (e.g., through visual cues like pointing to anatomic elements). In this work, we leverage a clinically-validated five-category classification of surgical feedback: "Anatomic", "Technical", "Procedural", "Praise" and "Visual Aid". We then develop a multi-label machine learning model to classify these five categories of surgical feedback from inputs of text, audio, and video modalities. The ultimate goal of our work is to help automate the annotation of real-time contextual surgical feedback at scale. Our automated classification of surgical feedback achieves AUCs ranging from 71.5 to 77.6 with the fusion improving performance by 3.1%. We also show that high-quality manual transcriptions of feedback audio from experts improve AUCs to between 76.5 and 96.2, which demonstrates a clear path toward future improvements. Empirically, we find that the Staged training strategy, with first pre-training each modality separately and then training them jointly, is more effective than training different modalities altogether. We also present intuitive findings on the importance of modalities for different feedback categories. This work offers an important first look at the feasibility of automated classification of real-world live surgical feedback based on text, audio, and video modalities.

Text-to-image diffusion models have been adopted into key commercial workflows, such as art generation and image editing. Characterising the implicit social biases they exhibit, such as gender and racial stereotypes, is a necessary first step in avoiding discriminatory outcomes. While existing studies on social bias focus on image generation, the biases exhibited in alternate applications of diffusion-based foundation models remain under-explored. We propose methods that use synthetic images to probe two applications of diffusion models, image editing and classification, for social bias. Using our methodology, we uncover meaningful and significant inter-sectional social biases in \textit{Stable Diffusion}, a state-of-the-art open-source text-to-image model. Our findings caution against the uninformed adoption of text-to-image foundation models for downstream tasks and services.

Meanwhile, there exists tremendous knowledge curated by humans in the text format describing proteins' high-level functionalities. Yet, whether the incorporation of such text data can help protein design tasks has not been explored. To bridge this gap, we propose ProteinDT, a multi-modal framework that leverages textual descriptions for protein design. ProteinDT consists of three subsequent steps: ProteinCLAP which aligns the representation of two modalities, a facilitator that generates the protein representation from the text modality, and a decoder that creates the protein sequences from the representation. To train ProteinDT, we construct a large dataset, SwissProtCLAP, with 441K text and protein pairs. We quantitatively verify the effectiveness of ProteinDT on three challenging tasks: (1) over 90% accuracy for text-guided protein generation; (2) best hit ratio on 10 zero-shot text-guided protein editing tasks; (3) superior performance on four out of six protein property prediction benchmarks. Machine learning (ML) has recently shown profound potential for protein discovery. These ML tools have been quickly adapted as auxiliary and accelerating roles in scientific pipelines, including but not limited to protein engineering [1], structure prediction [2], structure reconstruction [3], and inverse folding [4].