Methods for Molecular Modelling of Protein Complexes

Abstract

Biological processes are often mediated by complexes formed between proteins and various biomolecules. The 3D structures of such protein-biomolecule complexes provide insights into the molecular mechanism of their action. The structure of these complexes can be predicted by various computational methods. Choosing an appropriate method for modelling depends on the category of biomolecule that a protein interacts with and the availability of structural information about the protein and its interacting partner. We intend for the contents of this chapter to serve as a guide as to what software would be the most appropriate for the type of data at hand and the kind of 3D complex structure required. Particularly, we have dealt with protein-small molecule ligand, protein-peptide, protein-protein, and protein-nucleic acid interactions.Most, if not all, model building protocols perform some sampling and scoring. Typically, several alternate conformations and configurations of the interactors are sampled. Each such sample is then scored for optimization. To boost the confidence in these predicted models, their assessment using other independent scoring schemes besides the inbuilt/default ones would prove to be helpful. This chapter also lists such software and serves as a guide to gauge the fidelity of modelled structures of biomolecular complexes.

Keywords: 3D structure modelling; Molecular docking; Protein-biomolecular complexes; Scoring and sampling.