Research digital skills training 2021
Why are some molecules drugs?
Jóhannes Reynisson, School of Chemical Sciences
The fundamental question of why a few molecules are beneﬁcial drugs whereas most molecules are just molecules is still unanswered.
By calculating the properties of known drugs using quantum chemical methods a region of properties can be established and used as a metric for drug design. For example, by analysing drugs with different oral activity (how well can the drug be administered as a pill) and
calculating their polarisabilities and dipole moments it is clear that a preferred region is favoured as shown in Figure 1.
Figure 1: Dipole moment versus polarisability presenting the distribution of bioavailability groups with boundaries determined for Group. Group 1– low (red squares), group 2 – moderate (orange diamonds), group 3– high oral activity (green circles). In the range of 15-40 Å³ (polarisabilities) and 0.5 – 6 D (dipole moments) ~58% of high oral activity drugs are found meaning that this is a target area for designing new drugs with the ability to cross cell membranes.
Calculating the physiochemical properties of drug compounds
Having a computational resource such as the Pan cluster allows us to calculate the physicochemical properties of the drug compounds under study on a high level of theory. Gaussian software is used. A large host of drugs/ compounds need to be processed and the calculations required are computationally demanding. This is instrumental in deﬁning the boundaries of Known Drug Space and without the Pan cluster this research is not possible. The next challenge in our research is to use the polarised continuum model (PCM) to predict the water solubility of drug compounds and establish its boundaries. The PCM method is a sophisticated theoretical approach that requires substantial computational resource to process all known drugs.
Papers published with data generated with NeSI resources
1. P.A. Hume, M.A. Brimble, J. Reynisson, Aust. J. Chem., 65 (2012) 402-408.
2. P.A. Hume, M.A. Brimble, J. Reynisson, Comp. Theor. Chem., 1005 (2013) 9-15.
3. K.L.M. Drew, J. Reynisson, Eur. J. Med. Chem., 56 (2012) 48-55.
4. B. Yu, J. Reynisson, Eur. J. Med. Chem., 46 (2011) 5833-5837.