Modeling of the Inhibition of the Intermediate‐Conductance Ca²⁺‐Activated K⁺ Channel (IKCa1) by Some Triarylmethanes Using Quantum Chemical Properties Derived From Ab Initio Calculations

Abstract

Inhibition of the Intermediate-Conductance Ca 2 þ -Activated K þ Channel (IKCa1) by some Triarylmethane (TRAM) derivatives has been successfully modeled by using quantum chemical properties derived from Ab Initio calculations and Weighted Holistic Invariant Molecular (WHIM) descriptors. The predictive model was conducted by Partial Least Squares (PLS) method in combination with Genetic Algorithm (GA). Models with good predictivity were obtained both in cross-validation procedures and external test set predictions. Our results show that Highest Occupied Molecular Orbital (HOMO) energy, some electronic properties, and topological distributions are important parameters influencing the binding of TRAMs with IKCa1. In addition, our model identified some relevant patterns that can be useful for understanding the IKCa1 inhibitory process and the design of new blockers. 866

Predictive QSAR model confirms flavonoids in Chinese medicine can activate voltage-gated calcium (CaV) channel in osteogenesis

“…Ab initio derived electronic properties in combination with topological quantumchemical descriptors (i.e. "k2alpha", "Id", "IdwAverage", "Most+vePotential", "MomInertiaY" and "DeltaEpsi-lonC") were used to help to describe the electronic environment of the flavonoids and locate molecular regions responsible for given bioactivity of flavonoids on the CaV channel [26]. The type of descriptors used and the extent to which they could encode the structural features of the molecules that were correlated to the response were critical determinants of the quality of the QSAR model.…”