Lauren O Chisholm, Kona N Orlandi, Sophia R Phillips, Michael J Shavlik, Michael J Harms
A protein's sequence determines its conformational energy landscape. This, in turn, determines the protein's function. Understanding the evolution of new protein functions therefore requires understanding how mutations alter the protein energy landscape. Ancestral sequence reconstruction (ASR) has proven a valuable tool for tackling this problem. In ASR, one phylogenetically infers the sequences of ancient proteins, allowing characterization of their properties. When coupled to biophysical, biochemical, and functional characterization, ASR can reveal how historical mutations altered the energy landscape of ancient proteins, allowing the evolution of enzyme activity, altered conformations, binding specificity, oligomerization, and many other protein features...
December 22, 2023: Annual Review of Biophysics