Proteins and Their Interacting Partners: An Introduction to Protein–Ligand Binding Site Prediction Methods

Abstract

Elucidating the biological and biochemical roles of proteins, and subsequently determining their interacting partners, can be difficult and time consuming using in vitro and/or in vivo methods, and consequently the majority of newly sequenced proteins will have unknown structures and functions. However, in silico methods for predicting protein–ligand binding sites and protein biochemical functions offer an alternative practical solution. The characterisation of protein–ligand binding sites is essential for investigating new functional roles, which can impact the major biological research spheres of health, food, and energy security. In this review we discuss the role in silico methods play in 3D modelling of protein–ligand binding sites, along with their role in predicting biochemical functionality. In addition, we describe in detail some of the key alternative in silico prediction approaches that are available, as well as discussing the Critical Assessment of Techniques for Protein Structure Prediction (CASP) and the Continuous Automated Model EvaluatiOn (CAMEO) projects, and their impact on developments in the field. Furthermore, we discuss the importance of protein function prediction methods for tackling 21st century problems.

Computational chemical biology and drug design: Facilitating protein structure, function, and modulation studies

“…In this context, many computational methods have been developed to identify orthosteric sites, allosteric sites, and hot spots. In this section, we will summarize general binding site detection methods, allosteric site prediction methods, and hot spots identification methods, which can be categorized into sequence‐based methods and structure‐based methods …”

“…Compared to sequence‐based methods, structure‐based methods are more widely used. Most structure‐based methods can be classified into template‐based methods, geometry‐based methods, energy‐based methods, and miscellaneous methods . Template‐based methods take into consideration that homologous proteins share similar structures and biological functions.…”

“…In this section, we will summarize general binding site detection methods, allosteric site prediction methods, and hot spots identification methods, which can be categorized into sequence-based methods and structurebased methods. 85 Sequence-based binding site detection methods are based on the evolutionary conservation of functional sites.…”

“…Most structurebased methods can be classified into template-based methods, geometry-based methods, energy-based methods, and miscellaneous methods. 85,87 Template-based methods take into consideration that homologous proteins share similar structures and biological functions. Generally, it is necessary to find a template protein with known binding sites that are sufficiently similar to the target protein in structure and sequence.…”

Ensemble Architecture for Prediction of Enzyme‐ligand Binding Residues Using Evolutionary Information

“…Over many decades, with increasing number of resolved and available ligand‐enzyme complexes, attempts to understand these interactions using sequence and structure information have been made . As extensively reviewed in many studies, some of these are applicable for one or more groups of ligands,, and are therefore, categorized under the general approaches.…”