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Keywords:

  • Ab initio calculations;
  • GA-PLS;
  • IKCa1 channel inhibitors;
  • QSAR;
  • Quantum chemical properties;
  • Triarylmethanes;
  • WHIM descriptors

Abstract

Inhibition of the Intermediate-Conductance Ca2+-Activated K+ 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.