Abstract
A method (FILO, Field Interaction Ligand Optimization) for obtaining the optimal molecular interaction field was developed on the basis of the Simplex optimization procedure applied to a matrix of interaction energies obtained by performing a GRID computation on a suitable data set. The FILO procedure was tested on a set of nine HIV-1 protease inhibitors with known crystal structures. The results of FILO consist of the optimal molecular interaction field of a putative new ligand with optimal binding affinity. The final FILO model yields R 2 and R 2 CV values of 0.993 and 0.936, respectively, and finds eight negative and four positive interaction nodes for the OH probe taken as an example. The eight H bonding interactions pointed out by FILO identified well the binding site AA-residues Gly A27, Asp A29, water 501, Gly B48 and Asp A25 of HIV-1 protease.
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Melani, F., Gratteri, P., Adamo, M. et al. FILO (Field Interaction Ligand Optimization): A simplex strategy for searching the optimal ligand interaction field in drug design. J Comput Aided Mol Des 15, 57–66 (2001). https://doi.org/10.1023/A:1011178027463
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DOI: https://doi.org/10.1023/A:1011178027463