FILO (Field Interaction Ligand Optimization): A simplex strategy for searching the optimal ligand interaction field in drug design

A method (FILO, Field Interaction Ligand Optimization) for obtaining the op timal molecular interaction field was developed on the basis of the Simplex optimization procedure applied to a matrix of interaction energies obtaine d by performing a GRID computation on a suitable data set. The FILO procedu re was tested on a set of nine HIV-1 protease inhibitors with known crystal structures. The results of FILO consist of the optimal molecular interacti on field of a putative new ligand with optimal binding affinity. The final FILO model yields R-2 and R-CV(2) values of 0.993 and 0.936, respectively, and finds eight negative and four positive interaction nodes for the OH pro be taken as an example. The eight H bonding interactions pointed out by FIL O identified well the binding site AA-residues Gly A27, Asp A29, water 501, Gly B48 and Asp A25 of HIV-1 protease.