nach0-pc: Multi-task Language Model with Molecular Point Cloud Encoder

Recent advancements have integrated Language Models (LMs) into a drug discovery pipeline. However, existing models mostly work with SMILES and SELFIES chemical string representations, which lack spatial features vital for drug discovery. Additionally, attempts to translate chemical 3D structures into text format encounter issues such as excessive length and insufficient atom connectivity information. To address these issues, we introduce nach0-pc, a model combining domain-specific encoder and textual representation to handle spatial arrangement of atoms effectively. Our approach utilizes a molecular point cloud encoder for concise and order-invariant structure representation. We introduce a novel pre-training scheme for molecular point clouds to distillate the knowledge from spatial molecular structures datasets. After fine-tuning within both single-task and multi-task frameworks, nach0-pc demonstrates performance comparable with other diffusion models in terms of generated samples quality across several established spatial molecular generation tasks. Notably, our model is a multi-task approach, in contrast to diffusion models being limited to single tasks. Additionally, it is capable of processing point cloud-related data, which language models are not capable of handling due to memory limitations. These lead to our model having reduced training and inference time while maintaining on par performance.

BindGPT: A Scalable Framework for 3D Molecular Design via Language Modeling and Reinforcement Learning

Generating novel active molecules for a given protein is an extremely challenging task for generative models that requires an understanding of the complex physical interactions between the molecule and its environment. In this paper, we present a novel generative model, BindGPT which uses a conceptually simple but powerful approach to create 3D molecules within the protein's binding site. Our model produces molecular graphs and conformations jointly, eliminating the need for an extra graph reconstruction step. We pretrain BindGPT on a large-scale dataset and fine-tune it with reinforcement learning using scores from external simulation software. We demonstrate how a single pretrained language model can serve at the same time as a 3D molecular generative model, conformer generator conditioned on the molecular graph, and a pocket-conditioned 3D molecule generator. Notably, the model does not make any representational equivariance assumptions about the domain of generation. We show how such simple conceptual approach combined with pretraining and scaling can perform on par or better than the current best specialized diffusion models, language models, and graph neural networks while being two orders of magnitude cheaper to sample.

nach0: Multimodal Natural and Chemical Languages Foundation Model

Large Language Models (LLMs) have substantially driven scientific progress in various domains, and many papers have demonstrated their ability to tackle complex problems with creative solutions. Our paper introduces a new foundation model, nach0, capable of solving various chemical and biological tasks: biomedical question answering, named entity recognition, molecular generation, molecular synthesis, attributes prediction, and others. nach0 is a multi-domain and multi-task encoder-decoder LLM pre-trained on unlabeled text from scientific literature, patents, and molecule strings to incorporate a range of chemical and linguistic knowledge. We employed instruction tuning, where specific task-related instructions are utilized to fine-tune nach0 for the final set of tasks. To train nach0 effectively, we leverage the NeMo framework, enabling efficient parallel optimization of both base and large model versions. Extensive experiments demonstrate that our model outperforms state-of-the-art baselines on single-domain and cross-domain tasks. Furthermore, it can generate high-quality outputs in molecular and textual formats, showcasing its effectiveness in multi-domain setups.

A Prior of a Googol Gaussians: a Tensor Ring Induced Prior for Generative Models

Generative models produce realistic objects in many domains, including text, image, video, and audio synthesis. Most popular models---Generative Adversarial Networks (GANs) and Variational Autoencoders (VAEs)---usually employ a standard Gaussian distribution as a prior. Previous works show that the richer family of prior distributions may help to avoid the mode collapse problem in GANs and to improve the evidence lower bound in VAEs. We propose a new family of prior distributions---Tensor Ring Induced Prior (TRIP)---that packs an exponential number of Gaussians into a high-dimensional lattice with a relatively small number of parameters. We show that these priors improve Fr\'echet Inception Distance for GANs and Evidence Lower Bound for VAEs. We also study generative models with TRIP in the conditional generation setup with missing conditions. Altogether, we propose a novel plug-and-play framework for generative models that can be utilized in any GAN and VAE-like architectures.