Proteins are the most efficient nano-machines and perform a broad range of functions.All of the information necessary for function is encoded in 1-D sequences. Proteins exquisitely translate this code to fold and function, yet deciphering this encoded information remains an open challenge. We have developed a physics-based metric called the Dynamic Flexibility Index (DFI) to study the relation between sequence and protein function in order to decipher the 1-D sequence code. DFI quantifies the resilience of a given position to the perturbations occurring at various parts of a protein using linear response theory, mimicking the multidimensional response when the protein’s conformational space is probed upon interaction with small molecules or other cellular constituents. Using DFI, we have analyzed conformational dynamics of ancestral proteins and compared them with their modern counterparts to re-trace evolutionary steps for emergence of new function or adaptation to a new environment. This analyses have shown that protein static structures do not need to be modified in order for new function or molecular adaptation to emerge. Proteins may evolve and adapt new function by fine tuning their native state conformational dynamics. These studies provide us a molecular mechanism: <i>Nature utilizes minimum perturbation-maximum response as a principle through the allosteric alteration of the dynamics of the active/catalytic sites by mutating distal positions, rather than introducing mutations on active sites</i>. We also showed that this principle can be used to design proteins with desired function.

Conformational dynamics play critical role in protein evolution

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.