Neural potentials of proteins extrapolate beyond training data.

We evaluate neural network (NN) coarse-grained (CG) force fields compared to traditional CG molecular mechanics force fields. We conclude that NN force fields are able to extrapolate and sample from unseen regions of the free energy surface when trained with limited data. Our results come from 88 NN force fields trained on different combinations of clustered free energy surfaces from four protein mapped trajectories. We used a statistical measure named total variation similarity to assess the agreement between reference free energy surfaces from mapped atomistic simulations and CG simulations from trained NN force fields. Our conclusions support the hypothesis that NN CG force fields trained with samples from one region of the proteins' free energy surface can, indeed, extrapolate to unseen regions. Additionally, the force matching error was found to only be weakly correlated with a force field's ability to reconstruct the correct free energy surface.

Assessment of chemistry knowledge in large language models that generate code.

In this work, we investigate the question: do code-generating large language models know chemistry? Our results indicate, mostly yes. To evaluate this, we introduce an expandable framework for evaluating chemistry knowledge in these models, through prompting models to solve chemistry problems posed as coding tasks. To do so, we produce a benchmark set of problems, and evaluate these models based on correctness of code by automated testing and evaluation by experts. We find that recent LLMs are able to write correct code across a variety of topics in chemistry and their accuracy can be increased by 30 percentage points via prompt engineering strategies, like putting copyright notices at the top of files. Our dataset and evaluation tools are open source which can be contributed to or built upon by future researchers, and will serve as a community resource for evaluating the performance of new models as they emerge. We also describe some good practices for employing LLMs in chemistry. The general success of these models demonstrates that their impact on chemistry teaching and research is poised to be enormous.

A Perspective on Explanations of Molecular Prediction Models.

Chemists can be skeptical in using deep learning (DL) in decision making, due to the lack of interpretability in "black-box" models. Explainable artificial intelligence (XAI) is a branch of artificial intelligence (AI) which addresses this drawback by providing tools to interpret DL models and their predictions. We review the principles of XAI in the domain of chemistry and emerging methods for creating and evaluating explanations. Then, we focus on methods developed by our group and their applications in predicting solubility, blood-brain barrier permeability, and the scent of molecules. We show that XAI methods like chemical counterfactuals and descriptor explanations can explain DL predictions while giving insight into structure-property relationships. Finally, we discuss how a two-step process of developing a black-box model and explaining predictions can uncover structure-property relationships.

Model agnostic generation of counterfactual explanations for molecules.

An outstanding challenge in deep learning in chemistry is its lack of interpretability. The inability of explaining why a neural network makes a prediction is a major barrier to deployment of AI models. This not only dissuades chemists from using deep learning predictions, but also has led to neural networks learning spurious correlations that are difficult to notice. Counterfactuals are a category of explanations that provide a rationale behind a model prediction with satisfying properties like providing chemical structure insights. Yet, counterfactuals have been previously limited to specific model architectures or required reinforcement learning as a separate process. In this work, we show a universal model-agnostic approach that can explain any black-box model prediction. We demonstrate this method on random forest models, sequence models, and graph neural networks in both classification and regression.

Correction: Graph neural network based coarse-grained mapping prediction.

[This corrects the article DOI: 10.1039/D0SC02458A.].

Graph neural network based coarse-grained mapping prediction.

The selection of coarse-grained (CG) mapping operators is a critical step for CG molecular dynamics (MD) simulation. It is still an open question about what is optimal for this choice and there is a need for theory. The current state-of-the art method is mapping operators manually selected by experts. In this work, we demonstrate an automated approach by viewing this problem as supervised learning where we seek to reproduce the mapping operators produced by experts. We present a graph neural network based CG mapping predictor called Deep Supervised Graph Partitioning Model (DSGPM) that treats mapping operators as a graph segmentation problem. DSGPM is trained on a novel dataset, Human-annotated Mappings (HAM), consisting of 1180 molecules with expert annotated mapping operators. HAM can be used to facilitate further research in this area. Our model uses a novel metric learning objective to produce high-quality atomic features that are used in spectral clustering. The results show that the DSGPM outperforms state-of-the-art methods in the field of graph segmentation. Finally, we find that predicted CG mapping operators indeed result in good CG MD models when used in simulation.