Virtual Winter School on Computational Chemistry

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Computational medicinal chemistry

Dr. Robert J. Doerksen

Associate Dean, Graduate School
Associate Professor of Medicinal Chemistry, Department of BioMolecular Sciences
Research Associate Professor, Research Institute of Pharmaceutical Sciences
University of Mississippi, University, MS, USA

Video Recording


A wide variety of computational chemistry methods are useful in the search for new drugs. These approaches are collectively termed computational medicinal chemistry. A typical small molecule drug (molecular weight < 500 Da) needs to interact with or react with a protein target to achieve its useful pharmacological effect. Its path through the human body can also include changing protonation state, crossing lipid barriers, being carried by proteins, and undergoing metabolic transformations. A series of computational methods can be used to study the progress of a drug through the body in the various stages of pharmacokinetics and pharmacodynamics. Three-dimensional representations of both the drug and of what it interacts with are often helpful. For this, conformational search and methods to calculate and rank the relative energies of conformations are necessary. Many electronic structure properties of the drug molecule can be calculated, which can be used to characterize the molecule and predict its behavior. Protein modeling is also important to carry out, including effective use of experimental structural information. The conformations of drug and target can then be used in molecular docking which in turn can serve as a key step in virtual screening to find, from a database of known structures, drug hits with never-before-reported useful pharmacological activity at targets of interest. This presentation will include examples of best-practice application of these methods, such as for identifying selective protein kinase inhibitors or cannabinoid receptor ligands.


H Liu; LA Walker; NPD Nanayakkara; RJ Doerksen “Methemoglobinemia caused by 8-aminoquinoline drugs: DFT calculations suggest an analogy to H4B’s role in nitric oxide synthase,” Journal of the American Chemical Society, 133, 1172-1175 (2011). doi: 10.1021/ja107472c; PMID: 21244096

H Liu; A Dasmahapatra; RJ Doerksen “Computational study on the conformations of gambogic acid,” Chemical Physics Letters, 511, 405-412 (2011). doi: 10.1016/j.cplett.2011.06.035; PMID: 22991483

MAM Ibrahim; M Na; J Oh; RF Schinazi; TR McBrayer; T Whitaker; RJ Doerksen; DJ Newman; LG Zachos; MT Hamann “The significance of endangered and threatened plant natural products in the control of human disease,” Proceedings of the National Academy of Sciences of the United States of America, 110, 16832-16837 (2013). doi:10.1073/pnas.1311528110

KM Elokely; RJ Doerksen “Docking challenge: Protein sampling and molecular docking performance,” Journal of Chemical Information & Modeling, 53, 1934–1945 (2013). doi: 10.1021/ci400040d PMID: 23530568

H Liu; RY Patel; RJ Doerksen “Structure of the cannabinoid receptor 1: Homology modeling of the inactive state and enrichment study based on CB1 antagonist docking,” MedChemComm, 5, 1297-1302 (2014). doi: 10.1039/C4MD00121D

G Fu; P. Sivaprakasam; OR Dale; SP Manly; SJ Cutler; RJ Doerksen “Pharmacophore modeling, ensemble docking, virtual screening, and biological evaluation on glycogen synthase kinase-3β,” Molecular Informatics, 33, 610–626 (2014). doi: 10.1002/minf.201400044

X Wang; J Liu; P Pandey; J Chen; FR Fronczek; S Parnham; X Qi; RJ Doerksen; D Ferreira; H Sun; S Li; MT Hamann “Assignment of the absolute configuration of hepatoprotective highly oxygenated triterpenoids using X-ray, ECD, NMR J-based configurational analysis and HSQC overlay experiments,” BBA (Biochimica et Biophysica Acta) General Subjects, 1861, 3089-3095 (2017). doi: 10.1016/j.bbagen.2017.09.001

J Pressly; SM Mustafe; A Sahar; P Pandey; KK Roy; RJ Doerksen; BM Moore; F Park “Selective cannabinoid 2 receptor stimulation reduces tubular epithelial cell damage following renal ischemia-reperfusion injury,” accepted to Journal of Pharmacology and Experimental Therapeutics (11/2017). doi: 10.1124/jpet.117.245522 PMID: 29187590