Modeling 3D Protein Structure using Chimera and Modeller

Homology or comparative protein structure modeling is a complex process, but with the help of tools like Modeller, it becomes more accessible and efficient. It's fascinating how the program can automatically calculate a model with all non-hydrogen atoms based on an alignment of a sequence to be modeled with known related structures. The input to Modeller are restraints on the spatial structure of the amino acid sequence(s) and ligands to be modeled, and the output is a 3D structure that satisfies these restraints as well as possible. It's amazing how the program can derive restraints from various sources such as related protein structures, NMR experiments, rules of secondary structure packing, cross-linking experiments, fluorescence spectroscopy, image reconstruction in electron microscopy, site-directed mutagenesis, residue-residue and atom-atom potentials of mean force, and even intuition. The program can operate on various spatial features defined by atoms or pseudo atoms. However, Modeller only automatically derives the restraints from the known related structures and their alignment with the target sequence.

Chimera offers a user-friendly graphical interface to run Modeller, which can be accessed either locally or via a web service hosted by the UCSF RBVI. The Modeller program provides various types of calculations like comparative (homology) modeling and building parts of a protein without using a template. It's worth noting that Modeller can build missing segments de novo, or refine existing segments by generating additional possible conformations. Loop regions are the parts that usually require building or refinement. This is a simple video tutorial that demonstrates how to perform comparative or homology modeling of a protein's three-dimensional (3D) structure using UCSF Chimera and Modeller software. The Chimera software serves as a graphical user interface (GUI) for the command-line user interface (CUI) of Modeller software.