Energetically favorable binding site determination between two m

Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...

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364578, G01N 3353, G06F 1714

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058663436

ABSTRACT:
A `docking` method based on finite grid forcefield sampling makes use of fast evaluation of interaction energies between molecules, such as macromolecules and ligands. The forcefield used to calculate interaction energies utilizes a potential energy function composed of a 1/r dependent electrostatic term and a (6-12) Lennard-Jones term for Van der Waals interactions. Successful prediction of ligand position and determination of ligand-protein interaction enthalpy is done by mapping potential energy field components of one of the molecules onto a energy field component grids, and mapping interaction field components of another of the two molecules onto interaction component grids. By calculating a correlation between each potential energy field component grid and each interaction field grid, a plurality of grids of molecule binding energy values is obtained which represent a binding energy of the two molecules in the given relative rotation between the molecules for each relative translational positions in space between the molecules. At least one maximum of the binding energy values is determined and the relative translational positions for the maximum binding energy values are recorded. By rotating at least one of the molecules according to each relative rotation in a range of rotation, and by repeating the mapping for the rotated molecule and subsequently repeating the calculating and determining for each of the relative rotations, it is possible to select an energetically favorable one of the relative rotations and the relative translational positions to generate a position value for an energetically favorable binding site between the two molecules.

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