Project Computational Design and Synthesis of Drugs

Dit vak wordt in het Engels aangeboden. Omschrijvingen kunnen daardoor mogelijk alleen in het Engels worden weergegeven.

Doel vak

To gain insight and experience in the molecular modeling tools that
enable (rational) drug design and to examine and plan efficient routes
to synthesize conceived ligands.

Inhoud vak

In the post-genome era, an overwhelming amount of data describing the
molecular characteristics of the targets is becoming available. For
example, the structure of many proteins is being determined using X-Ray
analysis and NMR techniques. Furthermore, high-throughput screening
results in massive amounts of data that reveal the molecular properties
of the ligands that are able to have interaction with the drug targets.
In this project, several techniques that can help to translate this data
into novel ligands will be discussed and applied. Specific topics
include crystal structure analysis, the building of homology models,
docking of ligands, calculating binding free energy and affinity of
ligands for the protein, de novo structure generation, and pharmacophore
modeling. These techniques generate ideas for novel compounds. Because a
design that cannot be synthesized is by definition a useless design, the
synthetic feasibility is a key and integral part of the design process.
Therefore, it is important to be able to define a synthetic pathway for
the preparation of the designed compounds. In this project, this aspect
will be covered by lectures on the concept of retrosynthesis and on the
incorporation of some biologically relevant moieties, such as
heteroatoromatic scaffolds and known affinity-increasers. An online
retrosynthetic demonstration with a search engine sets the stage for a
case study. For a specific design, a versatile and robust synthesis
route has to be defined. A thorough literature search, in combination
with detailed study of the reactions involved will result in a report
that describes the suggested chemistry in detail.


Project basis: including lectures, tutorials, self study, assignments
and group-work on a case-study.

Teachers: Dr. M. Wijtmans, Dr. D.P. Geerke, Prof. Dr.
De Esch.


Written exam (50%), case study report (50%). Both the exam and the case
study report should be passed.

Vereiste voorkennis

Knowledge of basic organic chemistry.


Two eBooks contain several chapters of literature. These two books are:

Mason: Volume 4 of Comprehensive Medicinal Chemistry II:
Computer-Assisted Drug Design (Mason (Ed.).

Hoffmann: Elements of Synthesis Planning (Hoffmann (Ed))

These books are accessible through UBVU at all VU computers. The same
holds true for articles and the Reaxys search engine (vide infra). When
at home, turn on the VU-proxy
( and
accessibility to all these items is maintained.
The following book (Clayden) is not an eBook accessible through UBVU,
but it contains useful background literature on organic chemistry. All
students that received their FAR BSc degree at the VU possess this book.
It is suggested by us that such students could consider lending this
book to others if necessary.

Clayden: Clayden, Organic Chemistry, Oxford University Press, 2001.

In the remainder of the guide, a distinction is made between integral
literature and background literature.
Integral literature represents literature that is considered integral to
the topic and hence is exam material.
Background literature either constitutes material for certain
assignments or offers a wider or alternative discussion of the topic
that an interested student can read at his/her own leisure. Background
literature is not exam material.


E-var, mDDS-M-var

Algemene informatie

Vakcode X_432734
Studiepunten 6 EC
Periode P4
Vakniveau 400
Onderwijstaal Engels
Faculteit Faculteit der Bètawetenschappen
Vakcoördinator prof. dr. I.J.P. de Esch
Examinator prof. dr. I.J.P. de Esch
Docenten dr. M. Wijtmans
dr. D.P. Geerke

Praktische informatie

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