Proteins and Their Interacting Partners: An Introduction to Protein-Ligand Binding Site Prediction Methods with a Focus on FunFOLD3

Abstract

Proteins are essential molecules with a diverse range of functions; elucidating their biological and biochemical characteristics can be difficult and time consuming using in vitro and/or in vivo methods. Additionally, in vivo protein-ligand binding site elucidation is unable to keep place with current growth in sequencing, leaving the majority of new protein sequences without known functions. Therefore, the development of new methods, which aim to predict the protein-ligand interactions and ligand-binding site residues directly from amino acid sequences, is becoming increasingly important. In silico prediction can utilise either sequence information, structural information or a combination of both. In this chapter, we will discuss the broad range of methods for ligand-binding site prediction from protein structure and we will describe our method, FunFOLD3, for the prediction of protein-ligand interactions and ligand-binding sites based on template-based modelling. Additionally, we will describe the step-by-step instructions using the FunFOLD3 downloadable application along with examples from the Critical Assessment of Techniques for Protein Structure Prediction (CASP) where FunFOLD3 has been used to aid ligand and ligand-binding site prediction. Finally, we will introduce our newer method, FunFOLD3-D, a version of FunFOLD3 which aims to improve template-based protein-ligand binding site prediction through the integration of docking, using AutoDock Vina.

Keywords: Critical Assessment of Techniques for Protein Structure Prediction (CASP); Docking; Ligand-binding site prediction; Protein–ligand interactions; Template-based modelling.