Novel Integrative Protocol for Reconstructing Large Macromolecules using Atomic Force Microscopy Data and Computational Docking

Abstract

The drastic reduction of novel folds in proteins newly determined by x-ray crystallography suggests that large macromolecules are built from domains with already known structures. We have developed a novel integrative protocol that combines experimentally-measured topographic surfaces of single molecules with atomic coordinates of molecular constituents of large proteins or assemblies. Topographic surfaces are obtained using high-resolution atomic force microscopy (AFM) imaging. The present integrative method is based on real-space docking of macromolecular constituents beneath the experimental topographic surface.