How to Extend the Use of Grid‐Based Interaction Energy Maps from Chemistry to Biotopics

Abstract

Many computational tools routinely used in chemistry could successfully be applied to the biosciences since protein-protein and protein-ligand interactions are governed by the laws of chemistry. This paper shows that it is possible to extend the use of existing computational tools from their traditional application field (e.g. chemistry) to culturally-related research areas by the implementation of simple but well-designed utilities. In particular, a computational strategy obtained by combining GRID (the program originally designed by Peter Goodford, and now distributed by Molecular Discovery Ltd.) and BIOCUBE4mf (an application freely available at www.casmedchem.unito.it) was used to a) characterize the surface properties of the cavity of the Bacillus anthracis protective antigen heptameric prepore; b) suggest how to design mutagenesis experiments; c) quantitatively show the selectivity of the KvAP channel for K(+) over Na(+) ions and d) rationalize the pharmacokinetic behavior of 1,4-DHP third-generation drugs.

Molecular Interaction Fields (MIFs) to Predict Lipophilicity and ADME Profile of Antitumor Pt(II) Complexes

“…In particular, according to Pastor et al (23), we assumed that the presence of any water molecule in its observed crystallographic position was energetically favorable. In practice, we used GRID to calculate the MIFs for the water probe and BIOCUBE4mf (24) to select the regions satisfying energetic criteria (energy threshold). Results are shown in Fig.…”

3D-QSAR in Drug Design - A Review

“…While negative energy levels of the contours describe regions at which ligand binding should be favored, positive energy levels normally characterize the shape of the target. Some of the recent applications of the GRID method include determining energetically favorable binding sites and characterization of their surface properties [51], building predictive pharmacophore models [52], classification and comparison of ligand-binding sites [53], and rational design of potent inhibitors of influenza virus sialidase [54]. Many times GRID maps are also used as input descriptors in CoMFA, GOLPE or SIMCA for QSAR or 3D-QSAR analyses [55].…”

Antiproliferative activity of aroylacrylic acids. Structure-activity study based on molecular interaction fields

“…BICUBE [37] was used to extract isosurfaces from molecular interaction fields, obtained by GRID hydrophobic (DRY), hydrogen bond donor/hydrogen bond acceptor (OH2), and H probes. The last probe is used to characterize molecular shape, while DRY and OH2 probes are chosen to characterize hydrophobic and polar part of molecules, respectively.…”