Computer-Aided Molecular Design

Research
Current Projects
Coordinate files for B.subtilis RNA polymerase homology models New
- File 1
- File 2
Selected Publications

Research

Research in the Griffith computer-laboratory is concerned with the development of new methods in computer-aided molecular design.
Our work is by nature collaborative, utilising our methods and expertise in varied projects to enable the rational design of new bioactive small molecules.
Ultimately, the aim is always to develop new drugs.

Current Projects

Design and development of highly selective modulators of bioamine G-protein coupled receptors (GPCRs), such as α1-adrenoceptors (with Dr A Finch, Pharmacology).
The role of key structural regions in the structure and function of GPCRs (with Dr A Finch).
Design of novel anti-HIV/AIDS agents (with Associate Prof. P Keller at the University of Wollongong).
Molecular shape and conformations of heterocyclic molecules (with Dr R Crumbie at the University of Western Sydney).
Drug-DNA interactions (with Associate Prof. L Wakelin, Pharmacology).

Projects available for Honours Students:

Projects 1 and 2 are in collaboration with Dr A Finch (Pharmacology/SOMS) and Dr N Kumar (School of Chemistry): Design and synthesis of subtype selective modulators of α1-adrenergic and of 5HT1 serotonergic receptors.

Project 1
A computer-aided drug design project and will introduce the student to a variety of contemporary techniques: homology modelling, docking, pharmacophore development and database mining.
Project 2
A synthetic chemistry project and would suit a student with an interest in both medicinal chemistry and pharmacology.
Depending on the interests and background of the student(s), collaborative projects under the joint supervision of all three academics are also available, combining computer-aided design with some synthesis and some pharmacological characterisation.
Project 3
Design of HIV-1 reverse transcriptase inhibitors with a novel mode of action. This computer-aided drug design project will introduce the student to a variety of contemporary techniques: docking, molecular dynamics simulations, pharmacophore development and database mining.

Selected Publications

J. Garner, J. Deadman, D. Rhodes, R. Griffith, P. A. Keller: A New Methodology for the simulation of Flexible Protein – Ligand Interactions, J. Mol. Graphics Model., 26(1), 187-197, 2007.

C. P. Gordon, R. Griffith, P. A. Keller: Control of HIV through the inhibition of HIV-1 integrase: a medicinal chemistry perspective, Med. Chem., 3(2), 199-220, 2007.

I. J. A. MacDougall, R. Griffith: Selective pharmacophore design for α1-adrenoceptor subtypes, J. Mol. Graphics, Model., 25, 146-157, 2006.

I. J. A. MacDougall, P. J. Lewis, R. Griffith: Homology modelling of RNA polymerase and associated transcription factors from Bacillus subtilis, J. Mol. Graphics Model., 23(4), 297-303, 2005.

R. Griffith, T. T. T. Luu, J. Garner, P. Keller: Combining Structure-Based Drug Design and Pharmacophores, J. Mol. Graphics Model., 23(5), 439-446, 2005.

S. J. McGinty, A. Finch, R. Griffith, R. M. Graham, J. B. Bremner: Synthesis and biological evaluation of bicyclic and tricyclic substituted nortropan derivatives: discovery of a novel selective α1D-adrenergic receptor ligand, Bioorgan. Med. Chem., 12 (21), 5639-5650, 2004.

P. A. Keller, C. Birch, S. P. Leach, D. Tyssen, R. Griffith: Novel Pharmacophore Based Methods Reveal Gossypol as a Reverse Transcriptase Inhibitor, J. Mol. Graphics Model., 21 (5), 365-373, 2003.

J. B. Bremner, K. Castle, R. Griffith, P. A. Keller, D. D. Ridley: Mining the Chemical Abstracts Database with Pharmacophore-Based Queries, J. Mol. Graphics Model., 12(3), 185-194, 2002.

J. B. Bremner, R. Griffith and B. Coban: Ligand design for α1-Adrenoceptors, Curr. Med. Chem., 8, 607-620, 2001.

P. A. Keller, S. P. Leach, T. T. T. Luu, S. J. Titmuss and R. Griffith: Development of Computational and Graphical Tools for the Analysis of Movement and Flexibility in Large Molecules. J. Mol. Graphics Mod., 18, 235-241, 2000.

J. B. Bremner, B. Coban, R. Griffith, K. A. Groenewoud, and B. F. Yates: Ligand Design for α1-Adrenoceptor Subtype Selective Antagonists. Bioorgan. Med. Chem., 8, 201-214, 2000.

S. J. Titmuss, P. A. Keller, and R. Griffith. Docking Experiments in the Flexible Non-nucleoside Inhibitor Binding Pocket of HIV-1 Reverse Transcriptase. Bioorg. Med. Chem., 7(6), 1163-1170, 1999.

R. Griffith, J. B. Bremner: Modelling of Adrenoceptor Ligand Targets Based on Novel Medium-or Macro-Sized Fused Nitrogen Heterocyclic Systems. J. Comput.-Aided Mol. Des., 13, 69-78, 1999.

R. Griffith, B. F. Yates, J. B. Bremner, S. J. Titmuss: A Quantitative Investigation of the Transannular Amine-Ketone (N→C=O) Interaction in Medium-Sized Heterocycles , J. Mol. Graphics and Modelling, 15 (2), 91-99, 1997.

R. Griffith, J. B. Bremner, S. J. Titmuss: A Molecular Mechanics Study of the Transannular Amine - Ketone (N→C=O) Interaction in Medium-Sized Heterocycles, J. Comp. Chem., 18 (9), 1211-1221, 1997.

J. B. Bremner, B. Coban, R. Griffith: Pharmacophore Development for Antagonists at Alpha1 Adrenergic Receptor Subtypes, J. Comput.-Aided Mol. Des., 10, 545-557, 1996.

Renate Griffith

Assoc Professor Renate Griffith
Department of Pharmacology
Room M206, Wallace Wurth
T (02) 9385 1912
F (02) 9385 1059
E

Personal Research Profile

Computer-Aided Molecular Design

Research

Current Projects

Projects available for Honours Students:

Project 1

Project 2

Project 3

Selected Publications