The document discusses software for quantum-pharmacological investigations and calculations of drug properties. It describes molecular modeling programs like HyperChem and ChemOffice that can calculate properties through molecular mechanics, semi-empirical, and ab initio methods. The document also discusses molecular descriptors that can be calculated, like partial charges, electrostatic potential, HOMO/LUMO orbitals, and docking algorithms to model protein-ligand interactions.

1. SOFTWARE FOR QUANTUM-PHARMACOLOGICAL INVESTIGATIONS Reporters: Voloshin A., Nebesna T. Scientific adviser: prof. Chekman I. S. National O.O. Bogomolets Medical University Pharmacology and Clinical Pharmacology Department

9. Types of Calculations: C omparison Modern tendency: - Combine MM/QM calculations for macromolecules; - Ab initio calculations (geometry optimization and properties calculation for drugs) – HF or DFT; - Solvation of calculated molecules calculation of energy parameters for small organic molecules (drugs, neurotransmitters, metabolites) 28 h . HF ( 6-31G ) Ab initio geometry optimization of small organic molecules (drugs, neurotransmitters, metabolites) 20 min . PM3 Semi-empirical geometry optimization and calculation properties of macromolecules: proteins (enzymes, receptors), nucleic acid 22 sec . MM+ Molecular mechanics Application in quantum pharmacology Duration of Calculation (for Atenolol molecule) Method Type of calculation

11. Molecular Descriptors. Electrostatic potential The molecular electrostatic potential is the potential energy of a proton at a particular location near a molecule. Negative electrostatic potential corresponds to a attraction of the proton by the concentrated electron density in the molecules (colored in green). Positive electrostatic potential corresponds to repulsion of the proton by the atomic nuclei in regions where low electron density exists and the nuclear charge is incompletely shielded (colored in shades of violet).

13. Molecular Descriptors. Ionization potential (IP), Electronic affinities (EA), Electronegativity, Hardness, Softness, Electrophilicity index (Electronegativity) (Hardness) (Softness) (Electrophilicity index) Electrophilicity index Softness Hardness Electronegativity Calculated value Properties

16. Docking Block-Sheme

19. Conclusions Work with macromolecule : viewing Ras.Mol , docking - AutoDock ↓ Optimal basis: 6-31 G **(d, p) PCM – solvation model ↓ ММ + ( molecular mechanics ) АМ1, РМ3, ZINDO ( semiempirical calculations ) ab initio (non empirical calculations ) Programs HyperChem, GAMESS Geometry optimization ( in gas or aqueous media ) ↓ Creating of ligand molecule (2 D ⃗ 3D) – Programs HyperChem, ChemOffice