Validation of approximate nonempirical scoring model for menin-mixed lineage leukemia inhibitors

Abstract

Numerous empirical scoring schemes are arbitrary, yielding contradictory results for different protein inhibitor families. This study is aimed to validate the predictive potential of alternative nonempirical model of inhibitory activity based on first principle quantum chemical results for new class of small molecules targeting the menin-mixed lineage leukemia (MLL) interaction. Presented nonempirical interaction energy model comprising long-range electrostatic multipole and approximate dispersion terms is universal and computationally affordable, outperforming a number of commonly used empirical scoring functions, especially when combined with analysis of solvation energy.