In Silico Carborane Docking to Proteins and Potential Drug Targets

Abstract

The presence of boron atoms has made carboranes, C(2)B(10)H(12), attractive candidates for boron neutron capture therapy. Because of their chemistry and possible conjugation with proteins, they can also be used to enhance interactions between pharmaceuticals and their targets and to increase the in vivo stability and bioavailability of compounds that are normally metabolized rapidly. Carboranes are isosteric to a rotating phenyl group, which they can substitute successfully in biologically active systems. A reverse ligand-protein docking approach was used in this work to identify binding proteins for carboranes. The screening was carried out on the drug target database PDTD that contains 1207 entries covering 841 known potential drug targets with structures taken from the Protein Data Bank. First, for validation, the protocol was applied to three crystal structures of proteins in which carborane derivatives are present. Then, the model was applied to systems for which the protein structure is available, but the binding site of carborane has not been reported. These systems were used for further validation of the protocol, while simultaneously providing new insight into the interactions between cage and protein. Finally, the screening was carried out on the database to reveal potential carborane binding targets of interest for biological and pharmacological activity. Carboranes are predicted to bind well to protease and metalloprotease enzymes. Other carborane pharmaceutical targets are also discussed, together with possible protein carriers.

Probing the Structure of Lysozyme–Carbon‐Nanotube Hybrids with Molecular Dynamics

“…The shape complementarity algorithm of PatchDock39 was used to generate docking models of lysozyme and a (10,10) CNT, probably the most representative and studied carbon nanotube. The docking poses were rescored with FireDock,40 in a protocol recently validated for the study of interaction between proteins and fullerenes41 and carborane 42. MD simulations were performed at constant pressure (1 atm) and temperature (300 K) with the AMBER 11 MD package43 by using a 2.0 fs time step (the SHAKE algorithm44 was used to constrain the stretching of bonds involving hydrogen atoms).…”

“…The docking poses were rescored with FireDock, [40] in a protocol recently validated for the study of interaction between proteins and fullerenes [41] and carborane. [42] MD simulations were performed at constant pressure (1 atm) and temperature (300 K) with the AMBER 11 MD package [43] by using a 2.0 fs time step (the SHAKE algorithm [44] was used to constrain the stretching of bonds involving hydrogen atoms). Electrostatic interactions were calculated with the particle mesh Ewald method, [45] and threedimensional periodic boundary conditions were applied.…”

Engineering the Fullerene‐protein Interface by Computational Design: The Sum is More than its Parts

“…In Silico Generation of the Mutants . Experimental data from NMR and a docking protocol,,,,, recently validated for the study of interaction between proteins and nanoobjects were used to generate the initial coordinates of the adduct…”

“…between protein and C 60 as previously described ,,,,,. The lateral chain of the residue to be mutated is deleted in the pdb file and the Trp residue is added using the tleap module in antechamber .…”

Utilization of Boron Compounds for the Modification of Suberoyl Anilide Hydroxamic Acid as Inhibitor of Histone Deacetylase Class II Homo sapiens

“…The reason boron compounds are selected to be substituted at the ZBG and CAP is because the clinical trials have shown that consumption of boron may prevent cervical cancer caused by HPV [37, 39]. By consuming the boron content of 84.1 mg per day, it could prevent cervical cancer [40].…”