Foundations of Molecular Modelling
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- Versione italiana
- Academic year
- 2022/2023
- Teacher
- ANTONELLA CIANCETTA
- Credits
- 6
- Didactic period
- Secondo Semestre
- SSD
- CHIM/08
Training objectives
- The course aims at providing students with basic knowledge and skills of molecular modelling methods used for the identification of bioactive molecules. During the lectures real life examples of the application of molecular modelling tools mostly used in the pharmaceutical industry for lead identification will be presented.
Knowledge: Students will become familiar with the force field concept through the study of the equations at the basis of molecular mechanics and with basic concept of quantum mechanics through the study of the equations at the basis of the methods used for molecular property determination. The students will gain knowledge of the molecular modelling techniques used for small molecules and biomolecular target 3D structure prediction and for lead identification. The course will enable the students to familiarize with intermolecular forces underlying ligand-target complexes and computer visualization methods thereof.
Skills: The students will be able to recognize the fundamental equations of molecular and quantum mechanics and describe the energetic terms composing them. The students will be able to recognize ligand-based and structure-based drug design techniques and describe the algorithms at the basis of molecular modelling software packages. The students will be able to indicate the use of the most appropriate modelling techniques for lead identification depending on the specific needs and the available experimental data. The students will be able to analyse ligand-protein complexes and identify the intermolecular forces established in them. Prerequisites
- The course requires knowledge of basic notions of general chemistry, organic chemistry and biochemistry. The students should be able to:
a) recognize the most common functional groups in organic molecules and know their reactivity, protonation state, and tautomerism
b) recognize amino acid side chains and nucleobases
c) know physicochemical properties of organic molecules and biomolecules and the intermolecular forces they can establish Course programme
- The course will consist of 36 hours of theoretical lectures and cover all the topics listed in the syllabus divided in three main parts, as follows:
PART I: General concepts [9 hours]
- Molecular graphics and computer representation of organic molecules and biomolecules
- Molecular modelling, molecular mechanics and force fields
- Introduction to quantum mechanics and its application for small molecule property determination. Application Examples
PART IIa: Ligands [9 hours]
- Introduction to small molecule 3D structure prediction methods
- Small molecule energy minimization and conformational analysis techniques
- Introduction to pharmacophore model generation and compound library preparation for virtual screening. Application Examples
PART IIb: Targets [9 hours]
- Introduction to experimental techniques for 3D structure determination
- Computational techniques for 3D structure prediction. Application Examples
PART III: Ligand-Target Complexes [9 hours]
- Ligand-protein inter-molecular interactions: methods for their analysis and representation
- Guidelines for the choice of the molecular modelling method based on available experimental data
- Introduction to Structure-based e Ligand-based drug design methods. Application Examples Didactic methods
- The course consists of 36 hours of theoretical lectures in which the students will be presented with practical demonstrations of the use of free web-based molecular modelling software. The students will be provided with instructions to reproduce the procedures shown independently. Focus groups will be organised in which the students will be able to follow the tutorials on their own devices under the teacher’s guidance.
Learning assessment procedures
- The exam will be in the form of an oral interview in which the students will have to demonstrate knowledge of the molecular modelling techniques at the basis of the identification of molecules of pharmaceutical interest. Throughout the course, the students will be encouraged to create, discuss, and share pictures, models and diagram which presentation will grant access to a simplified exam. During the exam the student might be asked to: describe images, schemes, equations and diagrams showing ligand-target complexes; provide explanation of the molecular modelling techniques covered in the programme; recognize fundamental equations of molecular mechanics and quantum mechanics and the energetic terms comprising them.
Reference texts
- Instructional material provided by the instructor (articles and slides). Specific topics can be explored on the following textbooks:
G.L. Patrick - Chimica Farmaceutica. Napoli: Edises, 2015.
W. Leach - Molecular Modelling: Principles and applications. Ed. Addison Wesley Longman
C. J. Cramer - Essentials of Computational Chemistry, Theories and Models. Wiley: Chichester, 2002
