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I am interested in computational and theoretical approaches to (as well as in collaborations with experimentalists for) the following topics.
Current Topics
Protein-ligand interactions
Nonbonded forces govern the interactions of natural substrates or xenobiotics with proteins. We are studying such interactions for particular cases using docking, molecular dynamics, ab initio and binding energy calculations of various kinds. Some sample projects are:
Actin with latrunculins- S. A. Ahmed, P. R. Daga, J. J. Bowling, M. K. Mesbah, D. T. Youssef, S. Odde, S. I. Khalifa, R. J. Doerksen and M. T. Hamann "Structure Assignment and Actin Docking of a Latrunculin with a Highly Oxidized Thiazolidinone Ring ," Organic Letters, 9, 4773-4776 (2007).
Phosphodiesterase with spiroquinazolinones- P. R. Daga and R. J. Doerksen "Stereoelectronic Properties of Spiroquinazolinones in Differential PDE7 Inhibitory Activity," Journal of Computational Chemistry, 29, yyy (2008).
Farnesyltransferase with benzophenones- A. Xie, P. Sivaprakasam and R. J. Doerksen "3D-QSAR analysis of antimalarial farnesyltransferase inhibitors based on a 2, 5-diaminobenzophenone scaffold," Bioorganic & Medicinal Chemistry, 14, 7311 (2006).
Cyclin-dependent kinases with manzamines-
Glycogen synthase kinase-3 with manzamines- M. A. Ibrahim, A. G. Shilabin, S. Prasanna, M. Jacob, S. I. Khan, R. J. Doerksen and M. T. Hamann "2-N-Methyl Modifications and SAR Studies of Manzamine A," Bioorganic & Medicinal Chemistry, 16, xxx-yyy (2008).
Glycogen synthase kinase-3 with maleimides-
Enzyme-catalyzed reactions
We have selected several enzymes as drug targets for fighting various diseases (details to be posted later). We use computational approaches to construct realistic and dynamic models of the functioning of the enzymes in order to understand how they function (elementary reaction steps) and how to control their function in order to improve human health (understanding of existing drug action, if any, and design of new drugs):
- Molecular dynamics (MD)
- Car-Parrinello molecular dynamics (CPMD)
- Mixed CPMD/MD methods
Molecular modeling for understanding drug action and drug design
We use the many existing methods of computer-aided drug design, such as multidimensional QSAR, docking, conformational analysis, molecular dynamics, and quantum chemistry, and develop new methods for treating the following:
- Novel and affordable antimalarial agents
- Development of selective antagonists for opioid receptors
Arylamide and other antimicrobial amphiphilic oligomers and polymers
We calculate various properties, such as torsional potentials and chemical shifts, to aid in the design and prediction of novel effective and selective antimicrobials:
- Novel structures
- Torsions around amide bonds
- Force field development for polymers
Optical rotations for differentiating diastereomers
Novel betapeptides constrained by side chains
Interests and Prior Topics
- Polarization in liquids
- The structure and dynamics of promising catalyst clusters of methylaluminoxane (MAO) containing Cl
- An open trefoil knot system based on hexa-coordinated zinc
- Torsions and the absolute conformation of tetrazole amines
- Radical combustion reactions of C(3P) or C(1D) with C2H2 or H2S studied by static density functional and coupled-cluster theory and by ab initio molecular dynamics
- Quantifying the aromaticity of heterocycles
- Connections between polarizability and aromaticity
- Accurate properties of molecules: dipole, quadrupole, octopole moments; polarizabilities; geometries and vibrational spectra
- Structure and stabilities of BN-containing heterocycles
- Radical reactions studied by Car-Parrinello molecular dynamics
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