Protein language model powers accurate and fast sequence search for remote homology

Homologous protein search is one of the most commonly used methods for protein annotation and analysis. Compared to structure search, detecting distant evolutionary relationships from sequences alone remains challenging. Here we propose PLMSearch (Protein Language Model), a homologous protein search method with only sequences as input. With deep representations from a pre-trained protein language model to predict similarity, PLMSearch can capture the remote homology information hidden behind the sequences. Extensive experimental results show that PLMSearch can search millions of query-target protein pairs in seconds like MMseqs2 while increasing the sensitivity by more than threefold, and is comparable to state-of-the-art structure search methods. In particular, unlike traditional sequence search methods, PLMSearch can recall most remote homology pairs with low sequence similarity but sharing similar structures. PLMSearch is freely available at https://dmiip.sjtu.edu.cn/PLMSearch. ### Competing Interest Statement The authors have declared no competing interest.