Improvements, trends, and new ideas in molecular docking: 2012–2013 in review

Abstract

Molecular docking is a computational method for predicting the placement of ligands in the binding sites of their receptor(s). In this review, we discuss the methodological developments that occurred in the docking field in 2012 and 2013, with a particular focus on the more difficult aspects of this computational discipline. The main challenges and therefore focal points for developments in docking, covered in this review, are receptor flexibility, solvation, scoring, and virtual screening. We specifically deal with such aspects of molecular docking and its applications as selection criteria for constructing receptor ensembles, target dependence of scoring functions, integration of higher-level theory into scoring, implicit and explicit handling of solvation in the binding process, and comparison and evaluation of docking and scoring methods.

Reliability analysis and optimization of the consensus docking approach for the development of virtual screening studies

“…Docking is also largely used for hit identification, representing the main example of receptor-based virtual screening (VS) procedure: a docking-based approach is commonly reported in several successful VS studies, both alone and in combination with other computational strategies [4][5][6][7][8] . For these reasons, the exponential attention that docking is gaining over time, as proved by the number of novel docking procedures and scoring functions reported in literature only in the last few years, cannot be blamed [9][10][11][12][13][14][15][16][17][18][19][20] . However, the remarkable interest for docking and for the development of new and optimized approaches is mainly due to the fact that the prediction of the actual binding mode of a ligand into a protein target is still far from being an easy task.…”

Understanding the challenges of protein flexibility in drug design

“…Molecular docking, which aims at predicting and analyzing molecular complexes (see Fig. 1 for an example), is one of the most popular and diversified of these approaches [2]- [4].…”

“…Sampling and scoring engender different challenges, but have a combined influence on docking accuracy and performance [7], [8]. Issues related to scoring have been examined in numerous reviews [4]- [6], [9], [10], and will not be discussed here. Instead, the present paper focuses on sampling methods.…”

The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases—Part III: In-Silico Molecular Docking Investigations

“…It can also be used to identify potential inhibitors, substrates, activators or binding partners from compound libraries that contains few hundreds to millions of compounds. Several recent reviews on molecular docking have appeared [357][358][359][360], so molecular docking principles and approaches will not be covered here.…”

“…These limitations stem, mostly, from the inability of the scoring functions in molecular docking algorithms to account for local and global macromolecular dynamics, in addition to inability to accurately predict covalent interactions and solvent accessibilities: (1) in most cases the protein is modeled as a rigid structure without flexibility; (2) solvation of the active/binding site and of the ligand is usually excluded; (3) free-energy estimation of protein-ligand complexes is largely ignored [357,361,362]. Molecular docking methodology, cavity definition and search algorithms, and thermodynamic scoring functions continue to improve, however [363].…”