Mu.Ta.Lig - COST ACTION CA15135


5 December 2016


General information

Name: Claire
Surname: Shoemake
Cell phone number with international prefix: +356 99423449
Country: Malta
Affiliation: Dept. of Pharmacy, University of Malta
Gender: Female
Year of the PhD title:  2007
Personal web page: Not Applicable
Previous COST participation: Yes


List of 10 selected publications within last 5 years

1. Cassar M, Shoemake C, Azzopardi LM, Saliba C, Gutierrez G. de novo Design of Non-Steroidal Oestrogen Receptor Modulating Molecules using Maltanedienol as a Lead Molecule. International Journal of Drug Design and Discovery 2013; 4(1): 965-977.

2. Ciantar J, Shoemake C, Mangani C, Azzopardi LM, Serracino Inglott A. Optimisation of Tyrosine-based Lead Molecules capable of modulation of the Peroxisome proliferator-activated receptor gamma. International Journal of Pharmaceutical Sciences and Research 2012; 3(8): 2550-2561.

3. Farrugia DL, Shoemake C, Attard E, Azzopardi LM, Mifsud SJ. Investigative study on the angiotensin converting enzyme (ACE) inhibiting properties of the terpenoid extract of Crataegus monogyna using in silico models. Journal of Pharmacognosy and Phytotherapy 2013; 5(2): 34-37

4. Grima A, Shoemake C, Azzopardi LM, Serracino Inglott A. Optimisation of Abiraterone Based Non-Steroidal Lead Molecules. BioMirror 2012; 3(9): 1-8.

5. Micallef C, Shoemake C, Azzopardi LM. Creating a high-throughput screening database to propose ligands capable of modulating the HIV-1 protease receptor. Journal of AIDS and HIV Research 2013; 5(7):  224-234.

6. Pace Bardon C, Shoemake C, Azzopardi LM. Investigating the Anti-Oestrogenic Effect of p-Synephrine and de novo Design of Oestrogen Receptor Modulating Molecules. Biomirror 2013; 4(10): 6-13

7. Galea K, Shoemake C, Azzopardi LM. Investigating the Anti-Oestrogenic Effects of Ephedrine and de novo Design of Oestrogen Modulating Molecules. International Journal of Pharmaceutical Sciences and Drug Research 2013; 5(4): 152-157

8. Portelli S, Shoemake C, Azzopardi LM. In silico Identification of a Potentially Novel Binding Modality for Dicarbonyl Compounds Having 2(3H)-Benzazolonic Heterocycles Within the PPARg Ligand Binding Pocket: A de novo Design Study. Biomirror 2014; 5(1):1-7.

9. Zammit M, Shoemake C, Attard E, Azzopardi LM. The Effects of Anabasine and the Alkaloid Extract of Nicotiana glauca on Lepidopterous Larvae. International Journal of Biology 2014; 6(3):36-46

10. Caruana C, Shoemake C. A Structure-Based Drug Design Approach for the Identification of Novel Selective Cyclooxygenase-2 Inhibitors using Resveratrol Analogues as Lead Molecules. Biomirror 2015; 6(10): 100-113


Main skills and expertise (up to 5)

1. Natural Products
2.Molecular Database Creation
3.Principal Component Analysis
4.Molecular Dynamics
5. Linux


Main equipment/facilities available in the participants’ lab (up to 5)

1. SyByl



Short personal activity proposal for the COST Action CA15135 (max 1000 characters)

The following is an example of a project for which we are seeking funding. It is representative of the type of work my research group does and of the type of experience I could bring to this action.


Maltanedienol is the active principle of padina pavonica, a species of seaweed that is endemic to the Mediterranean Sea. This molecule has proven calcium fixation capabilities such that it is used as a food additive in for poultry in egg production where it allows chickens to stand upright for longer, and in prawn farming where the resultant stronger exoskeleton provides for more robust crustaceans which withstand handling better during export. Its structural similarity to 17-b Oestradiol made the oestrogen receptor a logical target for investigation in this respect, however in vitro studes have excluded this receptor from the calcium fixation pathway. The farnesyl pyrophosphate enzyme is the established target for the bisphosphonate class of drugs, with drug molecules such as alendronic and ibandronic acid known to modulate this enzyme with increased osteoclastic calcium deposition and increased bone turnover rate in post-menopausal women. Preliminary in silico studies have shown maltanedienol to bind with an affinity greater than that of the bisphosphonates to the farnesyl pyrophosphate synthase ligand binding pocket. The raison d’etre of this study may therefore be condensed into an atomic validation of an affinity of maltanedienol for the farnesyl pyrophosphate synthase enzyme, and into the design of novel maltanedienol analogues capable of similar modulation of this receptor. The study will proceed as follows:

1.       Identification of a high resolution pdb crystallographic deposition describing the farnesyl pyrophosphate enzyme bound to a bisphosphonate drug

2.       3D construction of a structurally optimised maltanedienol molecule in Sybyl

3.       Modelling of the pdb crystallographic deposition identified in 1 above such that the small bisphosphonate molecule is extracted from its cognate ligand binding pocket.

4.       Docking the maltanedienol molecule into the farnesyl pyrophosphate receptor ligand binding pocket and performing conformational analysis through allowing single bond rotations within a static ligand binding pocket

5.       Identification of the best 20 bound conformations of maltanedienol and utilisation of these scaffolds for quantification of ligand binding affinity (pKd) and Ligand Binding Energy (Kcalmol-1)

6.       Selection of the optimal conformer (that which combines the highest binding affinity and lowest binding energy scores) identified from the cohort of 20 in 5 above. This conformer will provide the scaffold for further molecular modelling.

7.       Generation of 2D  maps highlighting critical amino acid contact points between the bisphosphonate and maltanedienol and comparison between the two.

8.       Utilisation of the information obtained in 7 above and SAR data available in the literature to create seed structures  that retain the moieties critical for traditional binding and which are capable of sustaining novel growth (in LigBuilder) at alternative loci

9.       Evaluation of novel structures with dual emphasis on affinity and Lipinski Rule compliance (proposed in vivo bioavailability)

10.   Selection of optimal structures (hailing from different pharmacophoric famIlies from process 9

11.   Setting up a comparative molecular dynamics simulation using the AMBER software suite such that through the carrying out of principal component analysis, the dynamics of the bisphosphonate/maltanedienol farnesyl pyrophosphate synthase complexes could be compared.

12.   Promotion of those structures producing dynamics most similar to those of the bisphosphonates for in vitro assay



Work Group preference: score from 1 (preferred) to 4 (not preferred)

Work Group of the CA15135 COST Action Score
WG1: Development of new chemical entities 3
WG2: Selection of biological targets and assessment of biological data 2
WG3: Development of chemical databases 1
WG4: Development of Computational methods for multiple ligand design and discovery 4