Protein evolutionary divergence is not random. A simple comparison of homologous proteins shows clear patterns of differential conservation/variation at the levels of amino-acid sequence, 3D structure, and protein motion. For instance, the rate of sequence evolution varies among sites; protein structures diverge more at some sites than others, deforming along the same coordinates that govern the softest internal protein vibrations, and some protein vibrations are more variable than others.
Here, I will describe a simple biophysical model of protein evolution that integrates the divergence of sequence, structure, and motion; it models the mutational effects on structure, dynamics, and stability, and natural selection as a function of protein stability. Despite its simplicity, the model matches the observed patterns of evolutionary divergence very well.
I will show that, as we usually rightly assume, sequence patterns emerge mainly from selective constraints. In contrast, stability-based natural selection has almost no influence on the divergence of structures and motions. Thus, there is a basic difference: patterns of sequence variation among sites are due to selection, but patterns of differential conservation of structure and motion are mainly mutational.