Basics of Molecular Modelling of Drugs - GAPL014
Title: Základy molekulového modelování léčiv
Guaranteed by: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis (16-16190)
Faculty: Faculty of Pharmacy in Hradec Králové
Actual: from 2024
Semester: winter
Points: 0
E-Credits: 3
Examination process: winter s.:written
Hours per week, examination: winter s.:14/14, C+Ex [HS]
Capacity: unknown / unknown (unknown)
Min. number of students: unlimited
4EU+: no
Virtual mobility / capacity: no
Key competences:  
State of the course: cancelled
Language: Czech
Teaching methods: full-time
Level:  
Guarantor: doc. PharmDr. Jan Zitko, Ph.D.
Examination dates   Schedule   
Annotation -
The aim of the course is to acquaint students with basic methods of Computer Aided Drug Design (CADD). CADD methods are routinely used in the rational design of new biologically active compounds (drugs). Students will learn basic theoretical principles of modelling small molecules (drugs), biological structures (receptors) and their interactions. Emphasis will be placed on the practical application of these methods, which will be practised in seminars. The principle outcome of the course is to learn CADD methods and understand their principles and utilization. Absolvents of the course are supposed to be able to design and perform a simple CADD project. Themes: Drug targets, Structure of proteins, Information systems and databases, In silico prediction of physicochemical properties, Drug-receptor interactions, Experimental methods to study drug-receptor interactions, Rational design and development of drugs with known receptor (structure-based drug design), Molecular docking. Molecular dynamics, Rational design and development of drugs with unknown receptor (ligand-based drug design), Pharmacophore models, Case studies.
Last update: Zitko Jan, doc. PharmDr., Ph.D. (04.02.2025)
Course completion requirements -
Requirements to obtain the credits: Active participation in all seminars (absence is allowed only for serious reasons and will be solved individually), sufficient outcomes of the tasks solved in the seminars, and sufficient outcomes of the final project solved in the last seminar. Successful completion of the exam is defined as sufficient scoring in the written exam test.
Last update: Zitko Jan, doc. PharmDr., Ph.D. (04.02.2025)
Literature - Czech

Doporučená:

  • . . In Young, D. C.. Computational Drug Design: A Guide for Computational and Medicinal Chemists . : WILEY-VCH, 2009, s. -. ISBN 978-0-470-12685-1..

  • . . In Brown, Nathan. In silico medicinal chemistry : computational methods to support drug design . Cambridge: Royal Society of Chemistry, 2016, s. -. ISBN 978-1-78262-163-8..

Volitelná:

  • . . In Davis, Andrew Ward, Simon E. (eds.). The handbook of medicinal chemistry : principles and practice . Cambridge, UK: Royal Society of Chemistry, 2015, s. -. ISBN 978-1-84973-625-1..

Last update: prepocet_literatura.php (14.08.2025)
Teaching methods -

Teaching takes the form of lectures and seminars. Attendance at lectures is recommended. Knowledge from the lectures will be assessed through an exam test. The lectures are designed to prepare students for work in the following seminar. The seminars are intended for practical training in working with CADD programs. Attendance at seminars is mandatory.

Last update: Zitko Jan, doc. PharmDr., Ph.D. (04.02.2025)
Requirements to the exam -

Practical skills gained in seminars, theoretical knowledge from lectures.

Last update: Zitko Jan, doc. PharmDr., Ph.D. (04.02.2025)
Syllabus -
  • Drug targets. Structure of proteins and nucleic acids. The importance of specific amino acids for the structure of proteins and for the catalysis of biochemical reactions.
  • In silico prediction of 3D structure of proteins. Homology models and possibilities of their use. Creating a homology model, automated web services for creating homology models (incl. AlphaFold).
  • Rational approaches to design and development of new drugs. Combinatorial libraries. Chemical information systems and databases. Biological information systems and databases. Crystallographic databases. Critical assessment of 3D protein structures. Data mining from public sources.
  • Fundamental principles of modelling – molecular mechanics, force fields, quantum mechanics.
  • The importance of physicochemical properties for the action of drugs. Methods of in silico prediction of physico-chemical properties of compounds. In silico prediction of pharmacokinetic parameters, metabolism and toxicity of compounds.
  • Drug-receptor interactions, intermolecular forces, hydrogen bonds.
  • Experimental methods for monitoring drug-receptor interaction. X-ray crystallographic analysis, NMR experiments, radioligands, isothermal titration calorimetry, thermal shift assay.
  • In silico methods for predicting drug-receptor interaction. Molecular docking. Molecular dynamics.
  • Overview of molecular docking methods. Rigid docking, flexible docking. Search function, conformational sampling, scoring functions. Overview of common molecular docking software and comparison of their functions. Freely available software (AutoDock Vina, DOCK), commercially available programs, online docking services (servers).
  • Critical evaluation of results of molecular docking. Special applications of molecular docking - virtual screening (HTVS), blind docking, protein-protein docking, covalent docking.
  • Rational methods of design and development of drugs with known receptor (Structure-based drug design).
  • Rational methods of design and development of drugs with unknown receptor (Ligand-based drug design). Pharmacophore models.
  • De novo design methods – ligand growing, fragment linking, scaffold hopping.
  • Case studies. Examples of drugs developed with Computer-Aided Drug Design (CADD) methods.
Last update: Zitko Jan, doc. PharmDr., Ph.D. (04.02.2025)
Learning resources - Czech
E-learning Moodle: Základy molekulového modelování léčiv
https://dl1.cuni.cz/enrol/index.php?id=4846
Last update: Zitko Jan, doc. PharmDr., Ph.D. (04.02.2025)
Learning outcomes - Czech

Předmět Základy molekulového modelování léčiv navazuje na znalosti a dovednosti získané v oblastech: obecné a bioorganické chemie, organické chemie, biochemie, a farmaceutické chemie.
Studující po absolvování předmětu umí použít následující termíny (včetně jejich běžně užívaných zkratek) ve správném kontextu směrem k počítačovému modelování biologicky aktivních molekul: ligand, receptor, vazebné místo, intermolekulární interakce, vodíková vazba, iontová interakce, halogenová vazba, pi-pi interakce, hydrofóbní interakce, homologní model (proteinu), Ramachandranův diagram, konformace, AlphaFold, PDB, ChEMBL, PubChem, ZINC, CADD, structure-based drug design, ligand-based drug design, SBDD, LBDD, HTVS, de novo design, docking, molekulová dynamika, MD, molekulová mechanika, MM, kvantová mechanika, QM, silové pole, energetická minimalizace, RMSD, RMSF, QSAR, QSPR, farmakofor, molecular fingerprint, Tanimoto index.

Výsledky učení:
Studující na základě získaných znalostí a dovedností:

  • definují základní pojmy, principy a cíle počítačem podporovaného vývoje léčiv (CADD);
  • orientují se ve strukturách proteinů, typech vazeb a interakcích mezi léčivem a cílovou biologickou strukturou;
  • identifikují a popíší základní principy modelování malých molekul a biologických struktur (molekulová mechanika, kvantová mechanika);
  • použijí veřejně dostupné databáze a nástroje pro modelování 3D struktur biologických cílů a malých molekul;
  • provedou přípravu malých molekul a receptoru za účelem modelování;
  • provedou základní molekulární docking a vyhodnotí jeho výsledky pomocí skórovacích funkcí a vizualizačních nástrojů;
  • provedou vyhledávání potenciálních ligandů daného receptoru pomocí 3D farmakoforového modelu;
  • vysvětlí principy molekulové dynamiky a možnosti jejího využití pro studium interakcí léčivo–receptor;
  • navrhnou a vypracují jednoduchý CADD projekt.
Last update: Zitko Jan, doc. PharmDr., Ph.D. (24.03.2025)
Entry requirements -

The course requires basic knowledge of organic and bioorganic chemistry and a general understanding of the mechanism of action of drugs. Additionally, we expect basic computer skills (MS Windows, file management, zipping) and a basic level of English (terminology, using software that is not localized into Czech).

Last update: Zitko Jan, doc. PharmDr., Ph.D. (04.02.2025)