Motions are involved in most or all aspects of protein function and control. The goal of our work is a quantitative understanding of the relations among structure, dynamics, and function of proteins remains unchanged and challenging. Quantitative models and theories are particularly important at present because genetic engineering makes the construction of vastly modified proteins possible. It is likely that genetically modified proteins and modified small peptides will play an increasingly important role in medicine and pharmacology. The number of possible modifications is, however, so large that not even the age of universe is long enough for a systematic study. Models and theories with predictive power of protein dynamics and function would therefore have impact on all health-related disciplines. The approach chosen in the present work follows the path that has been successful in many areas of physics and chemistry: The first step is an investigation of the energy landscape of proteins or, in other words, the determination of the protein energy as a function of its conformation. The main tools in this study are flash photolysis with monitoring from the visible to midinfrared and Fourier transform infrared spectroscopy over extended ranges in time, temperature, pressure, and protein conditions. The structure of the proteins chosen, for instance, myoglobin and cytochrome P450, are well known and this first step connects structure and energy landscape. The second step explores the dynamics, the motions of the proteins. The approach here is the monitoring of spectroscopic markers after pressure and temperature jumps. The third step is the study of the effect of the motions on simple protein functions, such as the binding of carbon monoxide to heme proteins. To determine the effect, motions and function will be studied simultaneously and the result of blocked or changed motions will be explored. At every step, quantitative models with predictive power will be constructed. These models should yield both general concepts and protein specific statements.
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