Goals

Education purposes of the course

This course has two goals:

These two goals will be pursued through a series of six seminars that each come with associated texts, videos, and practical exercises.

The seminar	What you will learn
Drug docking. The computational core of in silico drug design is Drug Docking . The underlying idea is that small molecules are tested for their fitness for a binding site in a target (that normally is a protein).	The role of mobility of ligand and target; possibilities and limitations of today's methods and software; which Force Fields are being used, and how; the role of drug design in the overall drug design process.
Homology modelling. In most drug design studies the structure of the target (protein) is not yet known. In many cases Homology Modelling can be used to predict this structure.	Independent of the fine details of the methods, homology modelling always proceeds along a similar set of steps. These steps will be explained, together with their strengths and weaknesses. A large number of Force Fields is being used in homology modelling, and these will be discussed.
Structure validation. Homology models and experimental structures both contain errors. A large number of (mainly Force Field based) methods exists that can be used to detect these errors. Different experimental errors are made when different experimental techniques are being used, and the validation seminar will address this point.	Essential differences between X-ray and NMR (the two main techniques used for experimental structure determination) will be discussed. Their strong and weak points will be mentioned. Validation techniques, and the associated Force Fields will be discussed.
Energy calculations and dynamics. In the docking, homology modelling, and validation seminars you have heard that molecules are not rigid. Their mobility can be estimated using force field based methods.	This seminar discusses the Force Field used in Molecular Dynamics and Energy Minimisation techniques. This type of Force Field is also often used in Drug Docking projects.
Force Fields. Force Fields are a very common tool in in silico biology, chemistry, etcetera. In its simplest form a Force Field is an algorithm with the associated data that can be used to describe a system and often also to predict the future of that system.	In this seminar five types of Force Field will be discussed to illustrate the versatility of Force Field based methods.
"Nothing in Biology Makes Sense Except in the Light of Evolution" is a 1973 essay by the evolutionary biologist and Russian Orthodox Christian Theodosius Dobzhansky.	Homology modelling is the process by which the unknown structure of a protein can be predicted using is similarity to a homologous protein with known structure. Homology means having a common ancestor. Sequence alignment is at the basis of homology modelling. Sequence analysis techniques can tell us much more about alignments and some examples will be discussed.

And if you want to hear it differently, look at these older videos. The previous page overrules them, but they haven't lost validity. Some videos discuss exam questions... So, these videos are also a good way to start preparing for the exam.

Learning outcomes of the course

At the end of the course you are able to describe the following concepts their application in practice, and to relate them to each other.

• Drug design; the process and its role the in overall drug design process;
• Drug docking; the role of mobility of ligand and target and possibilities and limitations of today′s methods and software.
• Force Fields; which different types are being used, and how;
• Homology modeling; the (strengths and weaknesses of) the similar steps to predict the structure of a protein;
• Molecular Dynamics; for estimating mobility of proteins.
• Structure validation; the (strengths, weaknesses and differences of the) two main techniques used for determining protein structures (and thus making experimental errors) (X-ray and NMR).
• Sequence alignment; the concepts of evolution theory using techniques of (multiple) sequence alignment and analyses as example.

And if you want a motivator, look here.

Expectations

We want this course to provide an optimal educational experience.

You can expect from us that:

• we are closely involved in the course and in you learning Bioinformatics and do our best to make you enthousiastic;
• we try to help you find your own answers to your questions to develop your academic skills;
• we are accessible and open to your ideas and opinions. So please let us know what your comments, questions, feedback and ideas are;
• we communicate agreements and planning regarding the course clearly and well in time.

We expect from you that:

• you understand that you will not always get a quick and easy answer; the help can consist of a counter-question to help you find out things autonomously;
• you are a serious participant who plans the work for this course well. Please ensure that you are enrolled in the course (Blackboard) and read the E-mails that are sent from Blackboard to keep you up to date;
• you come to us with your questions and suggestions. That is the fastest way to solve problems or improve things;
• you do not disturb the lecturer and fellow students during lectures. So if you want to send text messages, make a telephone call, be at the computer or have a talk with your neighbour, please wait until the break and the leave the lecture room. You cal always view the lecture afterwards on the website.