The long term goal of molecular approaches to biology is to describe living systems in terms of the laws of chemistry and physics. The objective of the proposal is to increase our understanding of the fundamental aspects and the functional role of protein dynamics. Energy based methods, including molecular dynamics, minimization, and normal mode calculations, will be used. The multiminimum potential surface of the protein crambin will be investigated by determining the characteristics of the barriers between the minima. The role of solvent in the glass transition of proteins near 220K will be investigated by the use of nonequilibrium simulations. The femtosecond and picosecond dynamics of the CO ligand and the protein myoglobin after photodissociation will be calculated and the results compared with recent infrared measurements. The conformational changes that occur in many proteins involved in control and cellular signalling will be explored. Ras p21 (which acts as an on switch for cellular growth), the retinoic acid receptor (which is a transcription activator involved in differentiation) and GroEL (which is an allosteric protein that participates in in vivo protein synthesis) will be studied. The proposed research is of interest as an end in itself and as the basis for rational approaches to therapeutic agents.
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