Creation of a 2D and 3D molecular database using drugs used in obstetric,
gynaecological and urinary tract infections
Mariana Ellul, Claire Shoemake, Lilian M. Azzopardi
Department of Pharmacy, Faculty of Medicine and Surgery, University of Malta, Msida, Malta
email: mell0014@um.edu.mt
DEPARTMENT OF PHARM
ACY
UNIVERSI
TY OF MA
LTA
Department of Pharmacy
University of Malta
INTRODUCTION
AIMS
The teaching of medicinal chemistry and the demonstration
of its relevance to students represents an on-going challenge
for educators.¹ The development of innovative teaching
methods and educational media tools, allows educators to
embrace the challenge of teaching such a subject and has
consequently resulted in positive learning outcomes.
Pharmacy students who are well trained in medicinal
chemistry are more likely to become competent pharmacists
since this knowledge helps to make optimal patient-specific
therapeutic decisions.²
The scope of this study was the creation of a user validated
two– and three– dimensional molecular database that:
METHOD
5. In cases were crystallographic evidence was available on the protein
data bank, the binding modality of the drug docked with its cognate
receptor was depicted in VMD®6.
Phase 1
1. A datasheet was created using Microsoft Excel® and divided into a
number of rows and columns, representing relevant chemical details
about each particular drug found in Chapter 7 of the BNF, which
describes drugs used in obstetrics, gynaecology and urinary tract
infections.
2. The structure of each molecule to be included in the database was
identified from DrugBank®3, which is a database already available
online.
3. The 2D structures of these drugs were then drawn in Accelyrs® Draw4
4.1.
4. 3D structures of the included drug molecules were constructed in
5
Sybyl® and saved in mol2 format. These files were read into Jmol, an
open-source Java based application for interactive viewing of
molecular structures in 3D, also suitable for creating web pages.
RESULTS
Figure 1.1 below represents a snapshot of what is displayed once the database is accessed
through the University server. The database is very user friendly and contains the following
parameters: name of drug, therapeutic class, indications for use, dose, side-effects and
contra-indications. It also incorporates physicochemical properties namely PSA, AlogP, H
Donor count, H acceptor count and IUPAC name. The 2D images previously drawn using
Symyx® Draw 3.3 can also be viewed on the database.
 Highlights the structural nuances of drugs used in obstetric,
gynaecological and urinary-tract infections.
 Demonstrates
graphically, where applicable, their
relationships to the receptor whose effect they modulate in
vivo.
 Contains structural and physicochemical data regarding its
constituent molecules.
6. Physicochemical parameters pertaining to each drug molecule were
entered on the database, which was then mounted online for easy
access. These were generated from Accelyrs® Draw 4.1 after the planar
2D structures of the drug molecules were drawn and after research of
PDB entries were conducted.
Phase 2
The validity and actual utility of the molecular database was tested
through the implementation of a validation study, in the form of a
questionnaire, which was disseminated to all undergraduate
pharmacy students. Two sets of questionnaires were designed: the
‘pre-exposure questionnaire’ where the students completed the
questionnaire without using the database and the ‘post-exposure’
questionnaire where the database was used as an adjunct to
questionnaire completion.
The graph in Figure 1.3 shows the results of the 1st, 2nd, 3rd and 4th year
undergraduate pharmacy students for both sets of questionnaires. Maximum
possible score was 50. Comparison of the two data sets is indicative of the
improvement sustained by students in all years when the database was used as an
adjunct to questionnaire completion.
Fig. 1.3 Mean score vs course year
Figure 1.4 below demonstrates improvement sustained by students segregated by
year of study, following exposure to the molecular database. An improvement of 28,
26, 22 and 21 marks was recorded among students following the first to the fourth
year of study respectively, implying a progressive decline in improvement with
increased year of study.
Fig1.1. Snapshot of the molecular database
Fig1.2. 3D depiction of ritodrine hydrochloride
The 3D images of each drug were also included
in the database. They are available as links—
once clicked through the ‘View option’, the user
is redirected to a separate window which shows
renderings created by Sybyl and Jmol. The
structures are rotatable through 360°, thus
enhancing the user experience.
Fig 1.4 Knowledge improvement scores
CONCLUSION
The construction of a 2D and 3D database represents a viable route through which abstract concepts, such as those inherent to medicinal chemistry, may be rendered more tangible
for undergraduate pharmacy students. This study demonstrated that the use of computer-aided learning and visual aids, enhanced cognitive abilities of all students. The major limitation to the widespread use of such technology is undoubtedly expense. Consequently, access to these educational tools is often not universally available.
Reference(s)
1. Alsharif NZ et al. Instructional Model to Teach Clinically Relevant Medicinal Chemistry. Am J Pharm Educ. 2006 Aug; 4: 9
2. Kahn F et al. Medicinal Chemistry and the Pharmacy Curriculum. Am J Pharm Educ. 2011 Oct; 75(8): 161
3. Wishart DS et al. DrugBank: a knowledgebase for drugs, drug actions and drug targets. Available from: http://www.drugbank.ca/
4. Symyx Technologies, Inc. Accelrys (Symyx) Draw 4.1. Available from: http://accelrys.com/products/informatics/cheminformatics/draw/
5. SYBYL-X 1.2. Tripos International, 1699 South Hanley Rd., St. Louis, Missouri, 63144, USA .
6. Dalke A, Humphrey W, Schulten K. VMD - Visual Molecular Dynamics. J Molec Graphics. 1996; 14: 33-38.