Modelling the Structure and Interactions of Bioactive Molecules

Data

Official data in SubjectManager for the following academic year: 2020-2021

Topic

In this course the basic examination methods of theoretical chemistry will be discussed by the practical point of view in the frame of following subtopics: Methods of molecular modelling. Description of the forcefield, semiempirical, ab initio and density functional methods, advantages and disadvantages. Discovering the balance between the model ant the calculation methods. The algorithm of the choice of appropriate model and calculation method. Short description of the basic rules and mathematical background of theoretical chemistry. calculation of the electronic structure of atoms and molecules. Calculation the equilibrium conformations of molecules, the role of the entropy in the interactions of bioactive molecules and its calculation. Description of the correlation between the reactivity and the temperature. Examples at molecular level. Considering the molecular environment: explicit and implicit methods. Interesting examples and applications in pharmacy.

Lectures

• 1. 1 lecture Experimental results raise the necessity of quantum-chemical description of the structure of materials. Quantitization and related quantities (energy, momentum, spin). Simple mathematical descriptions. - Dr. Kunsági-Máté Sándor
• 2. 1 lecture Experimental results raise the necessity of quantum-chemical description of the structure of materials. Quantitization and related quantities (energy, momentum, spin). Simple mathematical descriptions. - Dr. Kunsági-Máté Sándor
• 3. 2 lecture Axiomatic description of the quantum theory. Atomic unit system. Overview on the exact and approximative solutions of the time - independent Schrödinger equation. - Dr. Kunsági-Máté Sándor
• 4. 2 lecture Axiomatic description of the quantum theory. Atomic unit system. Overview on the exact and approximative solutions of the time - independent Schrödinger equation. - Dr. Kunsági-Máté Sándor
• 5. 3 lecture Approximative solutions: the molecular mechanics methods. - Dr. Kunsági-Máté Sándor
• 6. 3 lecture Approximative solutions: the molecular mechanics methods. - Dr. Kunsági-Máté Sándor
• 7. 4 lecture Semi - empirical methods, advantages and disadvantages. - Dr. Kunsági-Máté Sándor
• 9. 5 lecture Conformation analysis, energy minimization algorithms. - Dr. Kunsági-Máté Sándor
• 11. 6 lecture Electronic structure of molecules. The chemical bonds, tipes of bonds. The structure of molecules, stereochemistry. - Dr. Kunsági-Máté Sándor
• 13. 7 lecture Modelling in comparison with the experiments, calculation of the enthalpy, entropy and their appropriate experimental values. - Dr. Kunsági-Máté Sándor
• 15. 8 lecture Molecular symmetry, point groups and the symmetry of molecular vibrations. - Dr. Kunsági-Máté Sándor
• 17. 9 lecture Interactions of the primycin, ergosterol and oleic acid as plasma membrane unit. - Dr. Kunsági-Máté Sándor
• 19. 10 lecture Modelling the interactions of bioactive molecules with molecular containers in accordance with molecular packing of drugs. - Dr. Kunsági-Máté Sándor
• 21. 11 lecture Quantum - chemical background of the rules in atomic and molecular spectroscopy. Rules of Raman and Infrared transitions and their relationship with the molecular symmetry. - Dr. Kunsági-Máté Sándor
• 23. 12 lecture Effective calculation methods to consider the molecular environment: Onsager-model, Polarizable Continuum Model - Dr. Kunsági-Máté Sándor
• 25. 13 lecture Examples: simple chemical reactions, calculation of the stability weak molecular complexes, conformation analysis. - Dr. Kunsági-Máté Sándor
• 27. 14 lecture Examples: modelling the systems possessing high symmetry and infinite volume. Crystals and polymers. - Dr. Kunsági-Máté Sándor

Practices

• 4. 4 practice : Geometry optimization and conformation analysis. Energy minimization algorythm mostly used in geometry optimization practice.
• 5. 5 practice: Calculation of the static potential energy surfaces of chemical reactions. Methods to determine the transition states associated to the chemical reactions. Activation energy and activation free enthalpy.
• 6. 6 practice Molecular dynamics methods, Monte-Carlo method and the Langevin model. The implicite consideration of the molecular environment.
• 7. 7 practice Modelling the elementary chemical reactions. Calculation of molecular dynamics. Determination of the rection rate using direct trajectory method.
• 8. 8 practice Methods for consideration of the solvents: the Onsager-model, and the Polarizable Continuum Model, PCM. Explicit consideration of the solvent molecules. The TIP3P model.
• 9. 9 practice Calculation of molecular parameters have significant importance in the practice. The QSAR and the molecular similarity - analysis.
• 10. 10 practice Examples: conformation analysis, bong length, bond angle and dihedral angles. The bipyridile and thionine molecules. Calixarenes and stereoisomers. Importance of hydrogen bonds in the stability of molecular geometries.
• 11. 11 practice Examples: interactions of molecules. Calculation of the host - guest interactions, calculations of interactions of calixarenes with neutral molecules based on pi-pi interactions.
• 12. 12 practice Examples : elementary dissociation reactions: dissociation of asymmetric olefines. Effect of melecular environment on the reaction rate.
• 13. 13 practice Examples: Interaction of Primycin and oleic acid. Calculation of the interaction energy in system possessing large numbers of electrons.
• 14. 14 practice E+xamples: dynamic processes: modelling the crystal growth.

Seminars

Reading material

Obligatory literature

P.W. Atkins: Physical Chemistry

Literature developed by the Department

Slides and notes. Scientific publications presented are also offered.

Notes

Slides and Summaries of lectures are available electronically

Recommended literature

Jensen_F.-Introduction_to_Computational_Chemistry_(2007)
Scientific papers, list will be given during the lectures

Conditions for acceptance of the semester

There is no possibility to make up for a missed lecture

Mid-term exams

Two tests, each above 60 % is required for acceptance

Making up for missed classes

Upto 15% is allowed, electronical material is available

Exam topics/questions

Methods of molecular modelling. Description of the forcefield, semiempirical, ab initio and density functional methods, avantages and disadvantages. The balance between the model ant the calculation methods. The algorithm of the choice of appropriate model and calculation method.Short description of the basic rules and mathematical background of theoretical chemistry. calculation of the electronic structure of atoms and molecules. Calculation the equilibrium conformations of molecules, the role of the entropy in the interactions of bioactive molecules and its calculation. Description of the correlation between the reactivity and the temperature. Examples at moecular level. Considering the molecular environment: explicit and implicit methods. Interesting examples and applications in pharmacy.

Examiners

Instructor / tutor of practices and seminars

• Dr. Kunsági-Máté Sándor