Post-translational modifications (PTMs) play an important role in various biological processes through changing protein structure and function. Some ultramodified proteins (like histones) have multiple PTMs forming PTM patterns that define the functionality of a protein. Top-down MS analyzes intact proteins and reveals PTM patterns along the entire proteins. MS-Align-E is a software tool for identifying ultramodified proteins with expected and unexpected PTMs using top-down mass spectrometry.