Faculty

Computer simulations provide a wide range of information about molecular behavior, enabling the description of motions of individual atoms, but the practical application of simulations is limited by the accuracy of the approximations, the difficulty in relating simulations to observable properties, and the insufficient length of feasible simulations relative to biochemically interesting time scales.

My research focuses on developing approaches to overcome these limitations and to applying the new methods to solve interesting chemical and biological problems.

Specific studies include simulations of conformational thermodynamics and dynamics in peptide and protein systems to correlate simulations with experimental data as well as between flexibility and reactivity of peptide drugs; use of free energy simulation methods to investigate effects of point mutations in proteins, including influence on ligand binding, oxidation, hydrophobic interactions, macromolecular solvation and aggregation; and rational design of receptors that will efficiently and specifically bind cationic ligands, which can be used for environmental waste remediation.

Our goals are to relate the detailed microscopic information provided by the simulations to observable, macroscopic physical, chemical and biological properties. Besides providing a basic understanding of biologically important molecules, the simulation results provide predictions on how to manipulate the properties for practical purposes. The work involves both using existing simulation programs and development of new methods and algorithms for molecular modeling.

Representative Publications

• J. Mahadevan, C. Xu, T. Siaahan and K. Kuczera, Molecular dynamics simulations of conformational behavior of linear RGD peptidomimetics and cyclic prodrugs in aqueous and octane solutions. J. Biomol. Struct. Dyn., (2002), 19:775–788.
• G. S. Jas and K. Kuczera, Free energy simulations of the oxidation of {C}-terminal methionines in calmodulin. Proteins, (2002), 48:257–268.
• C. Yang, G. S. Jas and K. Kuczera, Structure, dynamics and interactions with kinase targets: Computer simulations of calmodulin. Biochim. Biophys. Acta (2004) 1697:289–300.
• G. S. Jas and K. Kuczera, Equilibrium structure and folding of a helix-forming peptide: circular dichroism measurements and replica-exchange molecular dynamics simulations. Biophysical J. (2004) 87:3786–3798.
• Y. Houndonougbo, G. S. Jas and K. Kuczera, Structure and dynamics of phospholamban in solution and membrane bilayer: Computer simulations. Biochemistry (2005) 44:1780–1792.
• M. Wang, R. L. Schowen, R. T. Borchardt and K. Kuczera, Domain motions and the open-to-closed conformational transition of an enzyme: A normal mode analysis of S-adenosyl-L-homocysteine hydrolase. Biochemistry (2005) 44:7228–7239.
• M. Wang, J.R. Unruh, C. K. Johnson, R.L. Schowen, R.T. Borchardt and K. Kuczera. Effects of ligand binding and oxidation on hinge-bending motions in S-adenosyl-L-homocysteine hydrolase, Biochemistry, 45:7778-7786 (2006).
• S. Cai, Q.-S. Li, R. T. Borchardt, K. Kuczera and R. L. Schowen. The antiviral drug ribavirin is a selective inhibitor of S-adenosyl-L-homocysteine hydrolase from Trypanosoma cruzi. Bioorganic & Medicinal Chemistry,15:7281-7287 (2007).

Search PubMed for articles by Krzysztof Kuczera.