Performance of Radial Distribution Function-Based Descriptors in the Chemoinformatic Studies of HIV-1 Protease

Abstract

Aim: This letter investigates the role of radial distribution function-based descriptors for in silico design of new drugs. Methodology: The multiple linear regression models for HIV-1 protease and its complexes with a series of inhibitors were constructed. A detailed analysis of major atomic contributions to the radial distribution function descriptor weighted by the number of valence shell electrons identified residues Arg8, Asp29 and residues of the catalytic triad as crucial for the correlation with the inhibition constant, together with residues Asp30 and Ile50, whose mutations are known to cause an emergence of drug resistant variants. Conclusion: This study demonstrates an easy and fast assessment of the activity of potential drugs and the derivation of structural information of their complexes with the receptor or enzyme.

A new glimpse on the active site of SARS-CoV-2 3CLpro, coupled with drug repurposing study

“…At this distance, we identify atoms with dominant contributions to the g ( r = 8.8 Å). The dominant contribution is defined as a g ( r ) value larger than the mean g ( r ) contribution plus two standard deviations for a specific distance r [ 50 ]. Nitrogen atoms forming peptide bond from Glu166 and Met165, and peptide’s bond oxygen atom from Val186 are three atoms with a dominant contribution to 101, 99 and 94 complexes out of 109, respectively.…”

“…Briefly, the RDF vector, whose size is defined by the distance of its two most distant atoms ( r MAX ), represents each structure [ 50 , 57 ]. The elements of the vector are g ( r ) values, calculated in 0.1 Å intervals: a ij is the sum of atomic polarizabilities of atoms i and j , r ij the distance between atoms i and j , N is the number of atoms in a molecule and the preexponential factors p i and p j account for the number of outer electrons of the i -th and j -th atoms, correspondingly.…”

“…Ligands were excluded from calculations, to preserve consistency and for easier similarity index comparison. For more details see References [ 50 , 52 ].…”

“…In this paper, we calculated the recently introduced radial distribution function (RDF) weighted by the number of valence shell electrons [ 50 – 52 ] for 159 experimentally determined structures of SARS-CoV-2 3CLpro complexed with different ligands. The structural advantages of RDF, like it unambiguously describes 3D structures, its independence of the size of a molecule, and being invariant against translation and rotation of a molecule, are upgraded with electronic properties characteristic for each atom in a molecule.…”

Design, synthesis, antibacterial evaluation, and computational studies of hybrid oxothiazolidin–1,2,4‐triazole scaffolds

“…[60,[62][63][64] Recently introduced RDF descriptor weighted by the number of valence shell electrons (g(r)) was used to design QSAR model correlating it with the ligands' potential to inhibit DNA gyrase (IC 50 values). [65,66] For each optimized structure, hydrogen atoms were removed, and g(r) was (2)…”