Exploration of Conformations, Analysis of Protein and Biological Significance of Histidine Dimers

Abstract

The exhaustive conformational search of histidine dimers (HisD) carried out using density functional theory (DFT). A large number of non-covalent interactions and hydrogen bonding interactions stabilized various forms of HisDs that resulted 143 unique conformers. The HisDs which have hydrogen bonding interactions are more stable than other HisDs with aromaticaromatic interactions. In addition, search of HisDs in proteins that deposited in the protein data bank shows a significant increase of HisDs appear from 4 Å to 6 Å centroid-centroid distance. Further, the angle analysis between two p planes resulted that the number of dimers is more abundant at 318-608 angles which shows that HisD prefers tilted and parallel displaced orientations in the proteins. The above observations from protein data bank (PDB) analysis show good agreement with DFT calculations of the histidine dimers. In conclusion, the subtle balance between non-covalent interactions determine the conformational preferences of histidine dimers.Introduction:

Cumulative Millisecond-Long Sampling for a Comprehensive Energetic Evaluation of Aqueous Ionic Liquid Effects on Amino Acid Interactions

“…However, our results agree qualitatively with the PMF obtained for the parallel stacked histidine dimer investigated in ref 75, which reported slightly higher contact distances of 4.5 Å with a free energy of −1.1 kcal mol −1 , and quantummechanically determined interaction distances of antiparallelstacked dimers of histidine from ref 169 reporting CDs from 3.4 to 3.6 Å. 169 Notably, aIL overall showed no substantial effect on the location or depth of the minimum at the CD. In contrast, 2 M [Na/Cl] slightly increased the interaction strength by −0.4 kcal mol −1 .…”

“…Due to its multiple protonation states, its ability to act as H-bond donor or acceptor, and the possibility to participate in π–π- and cation−π-stacking interactions, , histidine is probably the most versatile of the 20 natural amino acids . Furthermore, apart from the role in protein folding and protein stability, , it is a crucial residue in many catalytic sites − and molecular recognition processes, resulting in histidine dimers frequently occurring in protein structures …”

“…Due to its multiple protonation states, 161 its ability to act as H-bond donor 162 or acceptor, 163 and the possibility to participate in π−πand cation−π-stacking interactions, 51,164 histidine is probably the most versatile of the 20 natural amino acids. 165 Furthermore, apart from the role in protein folding and protein stability, 51,164 it is a crucial residue in many catalytic sites 166−168 and molecular recognition processes, 169 resulting in histidine dimers frequently occurring in protein structures. 169 In general, the His−His interaction showed a similar-shaped PMF profile to the Phe−Phe interaction in water, with a global minimum at the CD of 3.6 Å with −2.6 kcal mol −1 and a stable SSM around 7 Å with −0.6 kcal mol −1 , separated by an energy barrier at 5.3 Å with a height of 1.5 kcal mol −1 , again indicating an energetically unbeneficial desolvation process upon binding.…”

“…165 Furthermore, apart from the role in protein folding and protein stability, 51,164 it is a crucial residue in many catalytic sites 166−168 and molecular recognition processes, 169 resulting in histidine dimers frequently occurring in protein structures. 169 In general, the His−His interaction showed a similar-shaped PMF profile to the Phe−Phe interaction in water, with a global minimum at the CD of 3.6 Å with −2.6 kcal mol −1 and a stable SSM around 7 Å with −0.6 kcal mol −1 , separated by an energy barrier at 5.3 Å with a height of 1.5 kcal mol −1 , again indicating an energetically unbeneficial desolvation process upon binding. However, our results agree qualitatively with the PMF obtained for the parallel stacked histidine dimer investigated in ref 75, which reported slightly higher contact distances of 4.5 Å with a free energy of −1.1 kcal mol −1 , and quantummechanically determined interaction distances of antiparallelstacked dimers of histidine from ref 169 reporting CDs from 3.4 to 3.6 Å.…”

In-silico study of seaweed secondary metabolites as AXL kinase inhibitors

“…Among the 1072 molecules screening top 100 hits were taken as cut-off of compounds with high binding affinities and further evolution of these top 100 molecules was carried out by structural visualization. The various non-covalent interactions play a significant part in the constancy of these protein–ligand complex stability ( Purushotham and Sastry, 2014 , Purushotham et al, 2012 , Uppula, 2018 ). Depending on the molecular docking conformation orientation in the site active further 100 molecules were reduced to the top 10 molecules.…”