The broad objectives of this work are to provide new computer simulation tools that will enable the detailed analysis of the role of molecular diffusion in biological processes at the subcellular and cellular levels, and the application of these tools to selected problems where close contact with experimental work is possible. The diffusional encounter of molecules with enzymes, antibody molecules, receptors, or other proteins; with membranes; or with nucleic acids is centrally involved in metabolism, immune and nervous system functions, signal transduction, cytoskeletal remodeling, gene expression, and a host of other processes in biology. The goals of the next project period will be to extend our simulation methods to allow the study of such processes, and to apply such simulation methods to selected problems with an emphasis on increasing scales of space and time. The methods will help in the development of antiviral agents, neurological drugs, and other materials of medical importance.
The specific aims for the next project period include the following, (a) New methods will be developed for the unified treatment of polar and apolar interactions of diffusing molecules, (b) Coarse-grained models will be developed for detailed description of the internal motions of biopolymers and their intermolecular interactions in diffusional processes, (c) Continuum simulation methods for molecular diffusion will be developed as a complement to the more familiar Brownian dynamics simulation methods, (d) Applications will be made to study crowding effects relevant to antiviral drug action, and to study diffusion and reaction of neurotransmitter in model synapses. The public health relevance of this work lies in the fact that the methods to be developed will be useful in the computer-aided design of Pharmaceuticals, including monoclonal antibodies that rapidly bind to and inactivate viruses, and drugs that act at multiple sites within synapses. Training of undergraduate, graduate and postdoctoral students for careers in public health will continue to be a key aspect of the project. ? ? ?
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