A protein's properties are influenced by both its amino-acid sequence and its three-dimensional conformation. Ascertaining a protein's sequence is relatively easy using modern techniques, but determining its conformation requires much more expensive and time-consuming techniques. Consequently, it would be useful to identify a method that can accurately predict a protein's secondary-structure conformation using only the protein's sequence data. This problem is not trivial, however, because identical amino-acid subsequences in different contexts sometimes have disparate secondary structures, while highly dissimilar amino-acid subsequences sometimes have identical secondary structures. We propose (1) to develop a set of metrics that facilitates better comparisons between dissimilar subsequences and (2) to design a custom set of inputs for machine-learning models that can harness contextual dependence information between the secondary structures of successive amino acids in order to achieve better secondary-structure prediction accuracy.

The cytochrome bc1 complex of the mitochondrial electron transport chain accomplishes the enzymatic reaction known as the modified Q-cycle. In the Q-cycle the bc1 complex transports protons from the matrix to the intermembrane space of the mitochondria, creating the proton gradient used to make ATP. The energy to move these protons is obtained by shuttling electrons from the coenzyme ubiquinol (QH2) to coenzyme ubiquinone (Q) and the mobile cytochrome c. This well studied complex is ideal for examining molecular adaptation because it consists of ten different subunits, it functions as a dimer, and it includes at least five different active sites. The program TreeSAAP was used to characterize molecular adaptation in the bc1 complex and identify specific amino acid sites that experienced positive destabilizing (radical) selection. Using this information and three-dimensional structures of the protein complex, selection was characterized in terms of coevolution and coadaptation. Coevolution is described as reciprocal local biochemical shifts based on phylogenetic location and results in overall maintenance. Coadaptation, on the other hand, is more dynamic and is described as coordinated local biochemical shifts based on phylogenetic location which results in overall adaptation. In this study both coevolution and coadaptation were identified in various locations on the protein complex near the active sites. Sites in the pore region of cyt c1 were shown to exhibit coevolution, in other words maintenance, of many biochemical properties, whereas sites on helix H of cyt b, which flanks the active sites Qo and Qi, were shown to exhibit coadaptation, in other words coordinated shifts in the specific properties equilibrium constant and solvent accessible reduction ratio. Also, different domains of the protein exhibited significant shifts in drastically different amino acid properties: the protein imbedded in the membrane demonstrated shifts in mainly functional properties, while the part of the complex in the intermembrane space demonstrated shifts in conformational, structural, and energetic properties.

Over the course of more than ten years, there has been a significant increase in the approach employed to inhibit the function of soluble epoxide hydrolase (sEH). The phenomenon of upregulating soluble epoxide hydrolase (sEH) has been found to result in a decrease in the ratio of epoxyeicosatrienoic acids (EETs) to dihydroeicosatrienoic acids (DHETs) in the body. This has garnered significant attention due to the diverse biological functions attributed to EETs, including the regulation of vasodilation, neuroprotection, increased fibrinolysis, calcium ion influx, and anti-inflammatory effects. Consequently, there has been a growing interest in developing and discovering sEH inhibitors through chemical syntheses and natural extracts, with the aim of increasing the availability of these anti-inflammatory molecules by reducing their hydrolysis. A comprehensive examination of this project was conducted to explore the inhibitory effects of YMSV, a tetrapeptide derived from the castor bean (Ricinus communis), on sEH, as well as to elucidate its underlying mechanism of action. YMSV was determined to function as a mixed-competitive inhibitor of soluble epoxide hydrolase (sEH), and the interaction between the peptide and the protein resulted in the disruption of the secondary structural composition of sEH. Furthermore, the hydrogen bond interactions between YMSV and the Asp 333 residue in the active region of soluble epoxide hydrolase (sEH) were demonstrated using molecular docking investigations. However, quantitative structure-activity relationship (QSAR) research revealed that nonpolar, hydrophobic, and bulky amino acids are favored at the N- and C- terminals of peptides for sEH inhibition. The results of this study indicate that peptides obtained from dietary sources possess unique characteristics as inhibitors of soluble epoxide hydrolase (sEH), displaying significant potency. Consequently, these peptides have promise for further development as therapeutic medicines targeting inflammation and depression in the future.