Reverse docking

Molecular docking has been a promising approach in lead discovery (2, 13) (also see discussion below). Reverse docking. 

Reverse docking druggability qq novo design library prediction... 

Fan S, Geng Q, Pan Z, Li X, Tie L, Pan Y, Li X (2012) Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach. BMC Syst Biol 6 152... 

Protein-ligand fingerprint similarity searches Contrarily to reverse docking and pharmacophore searches, protein-ligand fingerprints can be encoded in very simple bitstrings or real vectors, and do not necessitate true 3D information. 

There are three biochemical mechanisms of CYP inhibition competitive, mechanism-based, and metabolite-intermediate-complex (Fig. 5.3). Each type of inhibitor differs in the nature of CYP binding. Competitive inhibitors are reversibly bound and can be competed off of the docking site if another substrate of higher affinity is present at a higher concentration. Therefore,... 

Stereoselective catalysis using biocatalysts (e.g. enzymes) and also of rationally designed small chiral molecules, deals essentially with the same principle the spatial and selective docking of guest molecules to a chiral host molecule to form complementary interactions to form reversible transient molecule associates (see the specific sections in this volume). The enantiomeric excess of a certain reaction and hence the result will be determined by the degree of chiral discrimination. Along the same theoretical lines the concepts of protein (enzyme, antibody, etc.) mimicks via imprinted" synthetic polymers should be mentioned and will be discussed further. 

In a more recent continuation of these studies, Campiani and co-workers carried out semi-empirical calculations on a series of active compounds related to 2. This led to the identification of several structural and conformational features responsible for this activity <2005JME4367>. Docking into the human immunodeficiency virus 1 (HIV-1) reverse transcriptase non-nucleotide binding site (RT NNBS) of a compound of type 3 (X = O) highlighted that one of the phenyl rings of this compound protrudes toward the catalytic site <2005JME7153>. 

We tried to dock SFLLRN in a reverse manner to have the Arg side chain interact with Glu-347. However, in this mode there was no acidic residue for interaction with the N-terminal ammonium group and no hydrophobic pocket for Phe-43. 

Medina-Franco., J.L., Rodryguez-Morales, S., Juarez-Gordiano, C.A. Hernandez-Campos, A., Castillo. R. Docking-based CoMFA and CoMSIA Studies of Non-nu-cleoside Reverse Transcriptase Inhibitors of the Pyridinone Derivative Type. J. Comput.-Aided Mol. Des. 2004, 18, 345-360. 

La Regina, G., Coluccia, A., Di Pasquali, A., Silvestri, R. Docking and 3D QSAR Studies on Indolyl Aryl Sulfones. Binding Mode Exploration at the HIV-1 Reverse Transcriptase Non-nucleoside Binding Site and Design of Highly Active N-(2-Hydroxyethyl)carboxamide and N-(2-Hydroxyethyl)carbohydrazide Derivatives./. Med. Chem. 2005, 48, 213-23. 

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