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Review
. 2023 Jun 6:1-25.
doi: 10.1007/s00706-023-03076-1. Online ahead of print.

Molecular docking in organic, inorganic, and hybrid systems: a tutorial review

Madhuchhanda Mohanty  1 , Priti S Mohanty  1   2
Affiliations
Review

Molecular docking in organic, inorganic, and hybrid systems: a tutorial review

Madhuchhanda Mohanty et al. Monatsh Chem. .

Abstract

Molecular docking simulation is a very popular and well-established computational approach and has been extensively used to understand molecular interactions between a natural organic molecule (ideally taken as a receptor) such as an enzyme, protein, DNA, RNA and a natural or synthetic organic/inorganic molecule (considered as a ligand). But the implementation of docking ideas to synthetic organic, inorganic, or hybrid systems is very limited with respect to their use as a receptor despite their huge popularity in different experimental systems. In this context, molecular docking can be an efficient computational tool for understanding the role of intermolecular interactions in hybrid systems that can help in designing materials on mesoscale for different applications. The current review focuses on the implementation of the docking method in organic, inorganic, and hybrid systems along with examples from different case studies. We describe different resources, including databases and tools required in the docking study and applications. The concept of docking techniques, types of docking models, and the role of different intermolecular interactions involved in the docking process to understand the binding mechanisms are explained. Finally, the challenges and limitations of dockings are also discussed in this review.

Keywords: Density functional calculations; Donor–acceptor effects; Nanostructures; Natural products; Proteins.

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Figures

Fig. 1
Fig. 1
Receptor-ligand docked complex. Docking of a small molecule “Ligand” (cyan) to a bigger size molecule “Receptor” (yellow) to produce a stable docked complex. (Color figure online)
Fig. 2
Fig. 2
Different types of docking studies based on flexibility of receptors/ligands considered in molecular interaction. (Color figure online)
Fig. 3
Fig. 3
A A yellow dashed line rectangular docking box is created around the receptor’s whole surface. The whole surface is scanned for a possible binding pocket to dock with the ligand. The ligand is connected in the best binding site to make a stable complex. B The docking box is created around the receptor’s binding site surface. The ligand is connected to the binding site to make a stable complex. (Color figure online)
Fig. 4
Fig. 4
Different docking models: (1) Lock and key model, (2) Induced-fit model, (3) Conformational selection model. Among these three models, only induced-fit model induces a change in the shape of the binding pocket. (Color figure online)
Fig. 5
Fig. 5
Workflow of machine learning method in predicting protein–ligand interaction [46]. (Color figure online)
Fig. 6
Fig. 6
A Docked complex structure of spike protein fragment of coronavirus (SARS-CoV2) and human receptor angiotensin-converting enzyme 2 (ACE2) using molecular docking webserver ClusPro 2.2 [96, 97]. Spike protein fragment (331–524) is shown in red cartoon view, and human ACE2 is shown in blue cartoon view. B Docked complex structure of phytochemical “hesperidin” (ligand) and protein-enzyme bound structure of spike protein fragment of coronavirus (SARS-CoV2) and angiotensin-converting enzyme 2 (ACE2) (receptor) using SWISSDOCK web server and EADock DSS [97, 98] Spike protein fragment (331–524) is shown in red cartoon view, hesperidin molecule is shown in cyan and red stick view and human ACE2 is shown in blue cartoon view. C Docked complex structure of DNA with aflatoxin B1 exo-8,9-epoxide using AutoDock 4.0 [100, 101, 109]. Aflatoxin B1 exo-8,9-epoxide is shown in red stick view and DNA is shown in violet surface view [97, 101]. (Color figure online)
Fig. 7
Fig. 7
A Docked complex result of calf thymus DNA (CT-DNA) and G13 B Docking complex result of CT-DNA and EB using AutoDock Vina molecular docking tool [95, 102]. The DNA is represented in in cartoon view and both the ligands (G13 and EB) are shown in sticks view. H-bond is shown in green dashed line [102]. (Color figure online)
Fig. 8
Fig. 8
Molecular docking results with least binding energy between methylene blue (MB) cation (recognized as receptor) and organic polymer moieties (identified as ligands), namely carboxylate ion (COO−) (deprotonated), carboxylic acid (COOH) (protonated), and N-isopropylacrylamide (NIPAM) using AutoDock 4.2 tool with simulated annealing algorithm [100, 103, 104]. The polymer moieties and MB cationic dye are represented in ball-and-stick models and the inter-atomic distances (within 3.5 Å) between them are displayed in yellow dotted lines. MB, COO−, COOH, and NIPAM are colored blue, gray, dark gray, and black, respectively [103]. (Color figure online)
Fig. 9
Fig. 9
Column charts showing the total binding energy (BE), the contribution from different types of potential namely, electrostatics (EI), van der Waals-hydrophobic-desolvation (Vhd), tortional (T), and unbound (U) found in the docking result for the (COO−, MB), (COOH, MB), (NIPAM, MB) bound complexes [103]. (Color figure online)
Fig. 10
Fig. 10
A Docked complex structure of Hen egg white lysozyme (HEWL) protein in gold color cartoon view with water-coated iron nanoparticle (FeNP) in orange stick view using Hex 6.3 docking software tool [105, 107]. B Docked complex structure of VP6 trimer protein in grey cartoon and surface view with Pd(II) ion in blue sphere view at pH 5.0 using AutoDock 4.0 [100, 108]. The metal binding site is shown in red surface view containing polar residues His173, Ser240, and Asp242 viewed in red stick representation. C Docked complex structure of ubiquitin protein with bare neutral gold nano particle (AuNP) using Brownian dynamics (BD) rigid-body docking [106, 186]. The backbone of protein is shown in cartoon view and the residues those are in contact with the Au surface are shown in stick view and the rest of the atoms are shown in line view. The Au surface is shown in gold color net structure [107, 108, 186]. (Color figure online)
Fig. 11
Fig. 11
Best docking results with minimum binding energy after docking study between polymer moieties (COO−, NIPAM) with ions (Ag+, Au3+, and Fe2+) and atoms (Ag0, Au0, and Fe.0), respectively [111]. The polymer moieties, ions and atoms are represented in ball-and-stick, sphere, and sphere views, respectively. The distances between randomly chosen neighboring atoms of polymer moieties and ions are shown in yellow dashed line labelled in Angstrom unit (Å) [111]. (Color figure online)
Fig. 12
Fig. 12
Column charts that represent the contribution from different types of potential such as electrostatic (EI), van der Waals-hydrophobic (Vhd), and torsional(T) towards the net binding energy (BE) in docking studies between polymer moieties (COO−, NIPAM) with metal ions (Ag+, Au3+, and Fe2+) and atoms (Ag0, Au0, and Fe0) [111]. (Color figure online)
Fig. 13
Fig. 13
Organic–inorganic-hybrid MOF—organic dye molecule complex [112]. Complex structure of congo red dye (CR) (yellow color) with UiO-66 (a Zr (IV) based metal organic framework (MOF)) (gray and red) using ball-and-stick representation after docking study using AutoDock Vina [55, 95]. The active site is shown in cyan color ellipse [112]. (Color figure online)
Fig. 14
Fig. 14
Docked complex structure of zeolitic imidazole framework-8 (ZIF-8), a special class of metal organic framework (MOF) with organic molecule reactive blue-4 (RB4) ions using docking study with AutoDock Vina software [55, 95, 113]. ZIF-8 (receptor) and RB4 (ligand) are represented in stick and ball-and-stick models, respectively. H-bonds are represented with green and π–π interactions are shown with red dashed lines in the active site of ZIF-8 [113]. (Color figure online)
Fig. 15
Fig. 15
Docked complex structure of porous chromium terephthalate, MIL-101(Cr) and metronidazole (MNZ) using AutoDock 4 [114]. The MIL-101(Cr) (receptor) and MNZ (ligand) are viewed in stick and ball-and-stick models, respectively. For ligand, carbon, oxygen, sulfur, nitrogen, and hydrogen atoms are marked in green, red, yellow, blue, and orchid, respectively. For receptor, oxygen atoms and Cr ions are marked in red and orchid, respectively. The π–π interactions between imidazole rings of MIL-101(Cr) and MNZ, and hydrogen bonds are represented by pink and green dashed lines respectively in the binding site of MIL-101(Cr) [114]. (Color figure online)
Fig. 16
Fig. 16
Docked complex structure of UiO-66(Zr) metal organic framework (MOF) and chrysene (CRY), a toxic and hazardous polycyclic aromatic hydrocarbon (PAH) pollutant using AutoDock 4.2 [115]. UiO-66(Zr) MOF (receptor) and CRY (ligand) are shown in stick and ball-and-stick models, respectively. UiO-66(Zr) is marked in white, violet, and red color. Four benzene rings of CRY are marked in blue and light gray color [115]. (Color figure online)
Fig. 17
Fig. 17
Docked complex structure of two [Ag25(DMBT)18]− clusters using AutoDock 4.2 [100, 115]. Complex is shown in ball-and-stick model. Silver (Ag) and sulfur (S) atoms are shown in gray and yellow, respectively. C–H… π interactions are viewed in green dotted lines. Hydrogen (H) atoms and benzene rings associated with these interactions are viewed in red and blue, respectively. Other benzene rings not associated with these interactions are shown in green [116]. (Color figure online)
Fig. 18
Fig. 18
A Molecular docking complex of calf thymus DNA (CT-DNA) (PDB ID: 1BNA) and cobalt oxide (CoO) umbelliferone drug nanoconjugate using HEX 8.0.0 [117, 118]. DNA is represented in carton and surface view. The drug nanoconjugate, a mixture of CoO nanoparticle (blue and red sphered view) and umbelliferone drug (green, red, and white sphered view). B Non-covalent interactions of DNA bases with the nanoconjugate depicted by dashed lines [117]. (Color figure online)
Fig. 19
Fig. 19
A Docking result of human serum albumin (HSA) with the CoO-umbelliferone drug nanoconjugate by protein docking program, HEX 8.0.0 using Spherical Polar Fourier Correlations technique [–119]. B Binding interactions of noncovalent type between neighboring amino acid residues in the binding pocket of HSA and the drug nanoconjugate shown in dashed lines [117]. (Color figure online)
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