GRID force field

The interaction of drug molecules with biological membranes is a three-dimensional (3D) recognition that is mediated by surface properties such as shape, Van der Waals forces, electrostatics, hydrogen bonding, and hydrophobicity. Therefore, the GRID force field [5-7], which is able to calculate energetically favorable interaction sites around a molecule, was selected to produce 3D molecular interaction fields. 

Figure 12.2 The X-ray structure of human UGT2B7 (left) showing the UDPGA-binding site (left), and their molecular interaction fields (right) obtained using GRID force field [21], showing the large cavity and the hydrophilic regions (in blue).

The method is based on flexible MIFs generated by the GRID force field on the CYPs and UGThomology modeled structures that were treated and filtered to extract... 

Carosati, E., Sciabola, S. and Cruciani, G. (2004) Hydrogen bonding interactions of covalently bonded fluorine atoms from crystallographic data to a new angular function in the GRID force field. Journal of Medicinal Chemistry, 47, 5114-5125. 

Cruciani, G. and Watson, K.A. Comparative molecular field analysis using GRID force-field and GOLPE variable selection methods in a study of inhibitors of glycogen phosphorylase b. 

Structural Alignment Based on 3D Grid Force Field... 

Cruciani et al., used a dynamic physicochemical interaction model to evaluate the interaction energies between a water probe and the hydrophilic and hydrophobic regions of the solute with the GRID force field. The VolSurf program was used to generate a PLS model able to predict log Poet [51] from the 3D molecular structure. 

Cmciani, G., Watson, K. Comparative Molecular Field Analysis Using GRID Force Field and GOLPE Variable Selection Methods in a Study of Inhibitors of... 

The priorities of the people who create any MIF are a concrete manifestation of their scientific philosophy and overall objectives, and seven requirements seemed particularly important when the GRID force field [2] was being designed ... 

The GRID force field could have been calibrated either by using theoretical calculations, or by studying experimental observations, and after much discussion the experimental approach was adopted whenever possible. 

It is conventional to write impersonally about scientific research, but subjective decisions are made when one decides which features are worst, or which objectives are most important for a program. The personal pronoun we will therefore be used in this article, whenever it is appropriate to draw attention to subjectivity. We are still discussing priorities for the forthcoming release of GRID, but before describing the GRID force field in detail we must first describe how the GRID method actually works. 

One of the earliest decisions was to calibrate the GRID force field whenever possible by using experimental measurements rather than theoretical computations, and calorimetric measurements were therefore needed for the initial calibration in order to differentiate the enthalpic and entropic contributions to the overall free energy. However, only a very little calorimetric data was readily available at that time, about well characterised biological systems in which the structures of the interacting ligand and macromolecule were both known, and so a different approach was initially needed. 

E. Carosati, S. Sciabola, G. Cruciani, Hydrogen Bonding Interactions of Covalently Bonded Fluorine Atoms From Crystallographic Data to a New Angular Function in the GRID Force Field, J. Med. Chem. 2004, 47, 5114-5125. 

In principle, any method which is able to produce a molecular interaction field (MIF) could be applied to the characterization of the targets. However, almost exclusively the GRID program [19] has been used. This is due to the size of the problem which excludes the use of standard ah initio or semiempirical methods to produce interaction maps. It also reflects the many successful applications of the GRID force field in the characterization of protein active sites and the interpreta-... 

The program FLAP fits ligand molecules into a set of GRID MIFs of a protein structure. Thus FLAP can be used as docking program, which uses all the GRID force fields options and capabilities. 

Figure 4.4. Each pose for a given ligand (red structure) is then minimized inside the protein active site (purple structure) using the GRID force field.

The base theory underpinning TOPP is similar to the FLAP approach, previously described in this chapter. First, atoms in the molecules are classified by the GRID force field parametrization. In this way, atoms are described according... 

Sciabola, S., Baroni, M., Carosati, E., Cruciani, G. Recent improvements in the GRID force field. 1. The docking procedure GLUE, poster presented at the 15 Eur. Symp. QSAR Molecular Modelling, Istanbul, Turkey 2004. 

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