CH3716 – Quantitative Aspects of Medicinal Chemistry
Lecturers:
Dr T. van Mourik*, Professor T. K. Smith and Professor P. A. Wright
(*Module Convenor)
Aims:
The aim of the module is to cover some of the quantitative aspects of Medicinal Chemistry and drug design. Initially some relevant fundamental thermodynamics will be discussed. The thermodynamics of the drug receptor interactions will then be covered along with other aspects of pharmacology. The pharmacokinetic phase of drug action will be described including the absorption, distribution, metabolism and elimination (ADME) of drugs. The use of computational chemistry in the modern drug design process will then be discussed, covering force field calculations, molecular dynamics, molecular docking, QSAR (Quantitative Structure Activity Relationships) and pharmacophores.
Pharmacology and Pharmacokinetics – Professor T. K. Smith
Duration:
5 hours
Aims:
The aim of this part of the module is to cover some of the quantitative aspects of medicinal chemistry and drug design. Examples of past exam questions will be covered in the tutorial class.
Objectives:
1. Physical aspects of pharmacology, including drug-receptor interactions, receptor occupancy and dose response curves.
2. Derivation and use of the Schild equation.
3. The pharmacokinetic phase of drug action.
4. Discussion of the absorption, distribution, metabolism and elimination (ADME) of drugs.
5. Aspects of drug clearance and bioavailability.
6. Drug metabolism. The action of Phase 1 and Phase 2 enzymes.
7. The concept and design of pro-drugs.
Thermodynamics in Medicinal Chemistry – Professor P. A. Wright
Duration:
4 hours
Aims:
The course is intended to build on students’ knowledge of thermodynamics and solutions; to introduce some thermodynamic concepts relevant to solutions and to apply these to biochemically important phenomena such as osmosis and non-cooperative and cooperative ligand binding to proteins ligand binding at equivalent binding sites.
Objectives:
1. To understand the importance of Gibbs energy in medicinal chemistry and the concepts of partial molar quantities and chemical potential.
2. To understand osmosis, osmotic pressure and dialysis and their physiological and biochemical importance; to calculate solute molar masses; to recognise and deal with anomalies due to charge and solute molecular size, eg., proteins in solution and to understand the Donnan effect.
3. To understand how thermodynamic parameters reveal information on the physical processes involved in the binding reaction; to be able to use experimental data relating to the binding of ligands and metal ions to macromolecules to extract information on binding sites and dissociation constants.
4. To be familiar with experimental methods of obtaining binding parameters and thermodynamic data.
Computational Chemistry for Medicinal Chemists – Dr T. van Mourik
Duration:
6 hours
Aims:
The aim of this part of the module is to become familiar with computational chemistry techniques that are used in modern drug design processes, covering force field calculations, molecular dynamics, molecular docking, QSAR and virtual screening.
Objectives:
1. Introduction to computational chemistry for medicinal chemists, covering its use in the design and development of drugs, with practical examples.
2. To learn how molecular mechanics force fields are used in modelling.
3. To learn the basic concepts of molecular dynamics, including the calculation of thermodynamic properties.
4. To learn how molecular docking is used to predict whether a drug candidate will bind to its target receptor.
5. To understand the basics of QSAR (Quantitative Structure Activity Relationships), and how it is used to correlate chemical structure with biological activity.
6. To understand what pharmacophores are and how they can be used to identify lead compounds.