Scholar iON
Academic Synthesis
The body of research presented in these papers focuses on understanding the mechanisms and influences on protein folding, with particular attention to energetic frustration and pH-dependent behavior. Guzovsky et al. (2018) introduce a heuristic method to quantify local energetic frustration in proteins, identifying minimally frustrated regions as stable folding cores and highly frustrated sites as potentially functional areas like binding or active sites. Enciso et al. (2013) extend a coarse-grained simulation methodology to study the pH-dependent behavior of coiled coils, emphasizing how chain stiffness and length influence folding and unfolding transitions. Both studies contribute to a deeper understanding of protein dynamics, highlighting the importance of structural stability and environmental conditions in protein functionality and providing computational approaches validated against experimental data.
We present a detailed heuristic method to quantify the degree of local energetic frustration manifested by protein molecules. Current applications are realized in computational experiments where a protein structure is visualized highlighting the energetic conflicts or the concordance of the local interactions in that structure. Minimally frustrated linkages highlight the stable folding core of the molecule. Sites of high local frustration, in contrast, often indicate functionally relevant regions such as binding, active or allosteric sites.
In a recent work we proposed a coarse-grained methodology for studying the response of peptides when simulated at different values of pH; in this work we extend the methodology to analyze the pH-dependent behavior of coiled coils. This protein structure presents a remarkable chain stiffness andis formed by two or more long helical peptides that are interacting like the strands of a rope. Chain length and rigidity are the key aspects needed to extend previous peptide interaction potentials to this particular case; however the original model is naturally recovered when the length or the ridigity of the simulated chain are reduced. We apply the model and discuss results for two cases: (a) the folding/unfolding transition of a generic coiled coil as a function of pH; (b) behavior of a specific sequence as a function of the acidity conditions. In this latter case results are compared with experimental data from the literature in order to comment about the consistency of our approach.