We consider the protein sequence engineering problem, which aims to find protein sequences with high fitness levels, starting from a given wild-type sequence. Directed evolution has been a dominating paradigm in this field which has an iterative process to generate variants and select via experimental feedback. We demonstrate large language models (LLMs), despite being trained on massive texts, are secretly protein sequence optimizers. With a directed evolutionary method, LLM can perform protein engineering through Pareto and experiment-budget constrained optimization, demonstrating success on both synthetic and experimental fitness landscapes. Protein engineering aims to develop novel protein sequences exhibiting improved or new-to-nature functions (Romero & Arnold, 2009).

Large language models (LLMs) are having transformative impacts across a wide range of scientific fields, particularly in the biomedical sciences. Just as the goal of Natural Language Processing is to understand sequences of words, a major objective in biology is to understand biological sequences. Genomic Language Models (gLMs), which are LLMs trained on DNA sequences, have the potential to significantly advance our understanding of genomes and how DNA elements at various scales interact to give rise to complex functions. In this review, we showcase this potential by highlighting key applications of gLMs, including fitness prediction, sequence design, and transfer learning. Despite notable recent progress, however, developing effective and efficient gLMs presents numerous challenges, especially for species with large, complex genomes. We discuss major considerations for developing and evaluating gLMs.

We introduce M$^2$Hub, a toolkit for advancing machine learning in materials discovery. Machine learning has achieved remarkable progress in modeling molecular structures, especially biomolecules for drug discovery. However, the development of machine learning approaches for modeling materials structures lag behind, which is partly due to the lack of an integrated platform that enables access to diverse tasks for materials discovery. To bridge this gap, M$^2$Hub will enable easy access to materials discovery tasks, datasets, machine learning methods, evaluations, and benchmark results that cover the entire workflow. Specifically, the first release of M$^2$Hub focuses on three key stages in materials discovery: virtual screening, inverse design, and molecular simulation, including 9 datasets that covers 6 types of materials with 56 tasks across 8 types of material properties. We further provide 2 synthetic datasets for the purpose of generative tasks on materials. In addition to random data splits, we also provide 3 additional data partitions to reflect the real-world materials discovery scenarios. State-of-the-art machine learning methods (including those are suitable for materials structures but never compared in the literature) are benchmarked on representative tasks. Our codes and library are publicly available at https://github.com/yuanqidu/M2Hub.

We propose cKAM, cyclical Kernel Adaptive Metropolis, which incorporates a cyclical stepsize scheme to allow control for exploration and sampling. We show that on a crafted bimodal distribution, existing Adaptive Metropolis type algorithms would fail to converge to the true posterior distribution. We point out that this is because adaptive samplers estimates the local/global covariance structure using past history of the chain, which will lead to adaptive algorithms be trapped in a local mode. We demonstrate that cKAM encourages exploration of the posterior distribution and allows the sampler to escape from a local mode, while maintaining the high performance of adaptive methods.