DPAM-AI: A Domain Parser for AlphaFold Models Powered by Artificial Intelligence.

Abstract

Due to the breakthrough in protein structure prediction by AlphaFold, the scientific community has access to 200 million predicted protein structures with near-atomic accuracy from the AlphaFold protein structure DataBase (AFDB), covering nearly the entire protein universe. Segmenting these models into domains and classifying them into an evolutionary hierarchy hold tremendous potential for unraveling essential insights into protein function. We introduce DPAM-AI, a Domain Parser for AlphaFold Models based on Artificial Intelligence. DPAM-AI utilizes a Convolutional Neural Network trained with previously classified domains in the Evolutionary Classification Of protein Domains (ECOD) database. DPAM-AI integrates inter-residue distances, predicted aligned errors, along with sequence and structural alignments to previously classified domains detected via sequence (HHsuite) and structural (DALI) similarity searches. DPAM-AI has demonstrated its power through rigorous tests, excelling in several benchmark sets compared to its predecessor, DPAM, and to other recently published domain parsers, Merizo and Chainsaw. We applied DPAM-AI to representative AFDB models for proteins classified in Pfam. We obtained representative 3D structures for 18,487 (89%) of the 20,795 Pfam families, the remaining families either (1) belong to viral proteins that were excluded from AFDB or (2) do not adopt globular 3D structures. Our structure-aware domain delineation met uncovered a considerable fraction (15%) of Pfam domains containing multiple structural and evolutionary units and refined the boundaries for over half of them. The Pfam domains and their corresponding DPAM-AI domains are available at http://prodata.swmed.edu/DPAM-pfam/. Our code is deposited at https://github.com/Jsauce5p/DPAM/tree/dpam_ai, and updates will be released through https://github.com/CongLabCode/DPAM. No supplementary data are available.