Importance of Inter-residue Contacts for Understanding Protein Folding and Unfolding Rates, Remote Homology, and Drug Design.

Inter-residue interactions in protein structures provide valuable insights into protein folding and stability. Understanding these interactions can be helpful in many crucial applications, including rational design of therapeutic small molecules and biologics, locating functional protein sites, and predicting protein-protein and protein-ligand interactions. The process of developing machine learning models incorporating inter-residue interactions has been improved recently.

Long-Range Contacts in Unfolding of Two-State Proteins.

Predicting the unfolding rates of proteins remains complicated due to the intricacy present in the unfolding pathway of proteins and further it was observed that the experimental unfolding data were less while compared to folding kinetics. The aim of our present work is to show the variation in long-range contacts observed in various sequence separation bins belonging to all-α, all-β and mixed structural classes of 52 two-state proteins. In this work linear regression technique have been used and regression equations were developed using long-range contacts observed from various sequence separation bins.

Preferential water exclusion in protein unfolding.

Association of water with protein plays a central role in the latter's folding, structure acquisition, ligand binding, catalytic reactivity, oligomerization, and crystallization. Because these phenomena are also influenced by the net charge content on the protein, the present study examines the association of water with cytochrome c held at different pH values so as to allow its side chains to ionize to variable extents. Equilibrium unfolding of differently charged cytochrome c molecules in water-methanol binary mixtures, where the alcohol acts as the cosolvent denaturant, was used to quantify the preferential exclusion of water during the unfolding transition.

Sequence and structural analysis of two designed proteins with 88% identity adopting different folds.

Protein folding is a natural phenomenon by which a sequence of amino acids folds into a unique functional three-dimensional structure. Although the sequence code that governs folding remains a mystery, one can identify key inter-residue contacts responsible for a given topology. In nature, there are many pairs of proteins of a given length that share little or no sequence identity.