Professor Karplus is supported by a grant from The Theoretical and Computational Chemistry Program to use theoretical methods, including quantum and statistical mechanics, supplemented by computer simulations, to study solvation and properties of macromolecular systems of biological interest. Specific areas which will be studied include: 1) Solvation thermodynamics of intermediate-sized molecules, including polyenes, model peptides, and reactive systems. 2) Properties of macromolecular systems, including an extension of the methodology which employs simulated annealing for NMR and X-ray structure determination. 3) Enzyme catalysis studies which incorporate quantum mechanical calculations, molecular dynamics simulations, and free energy perturbation methods to investigate detailed events in catalysis by enzymes. 4) Ion transfer through the gramicidin channel using free energy perturbation methods and activated dynamics simulations.
