Toward Simple, Predictive Understanding of Protein-Ligand Interactions: Electronic Structure Calculations on Torpedo Californica Acetylcholinesterase Join Forces with the Chemist's Intuition.

ABSTRACT: Contemporary efforts for empirically-unbiased modeling of protein-ligand interactions entail a painful tradeoff - as reliable information on both noncovalent binding factors and the dynamic behavior of a protein-ligand complex is often beyond practical limits. We demonstrate that information drawn exclusively from static molecular structures can be used for reproducing and predicting experimentally-measured binding affinities for protein-ligand complexes. In particular, inhibition constants (K_i) were calculated for seven different competitive inhibitors of Torpedo californica acetylcholinesterase using a multiple-linear-regression-based model. The latter, incorporating five independent variables - drawn from QM cluster, DLPNO-CCSD(T) calculations and LED analyses on the seven co

SUBMITTER: Sylvetsky N 

PROVIDER: S-EPMC7280257 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature