Measuring and locating the changes in protein structure using MELO.

Abstract

Understanding the impact that subtle variations (missense mutation, environmental change, ion chelation, ligand binding, etc.) have on protein structure helps to reveal their biological effects, but remain extremely challenging due to the difficulty in measuring and locating the changes in protein structure. Herein, a method entitled MELO is therefore constructed, which enable a systematic measurement based on residues' geometric characteristics & relative distance and a high-throughput location of structural change based on secondary structure variation & protein segment shift. Our method performs best in capturing the structure changes of various degrees of magnitude (some increases were >30%) and is capable of precisely locating the regions of alterations for critical case studies. Moreover, it identifies over 10,000 structural changes induced by subtle variation that existing methods fail to detect. An online server allows users to upload their structures for comparison, and all those structural changes identified in this study have also been made available for download.