scholarly journals Structural and functional impact of non- synonymous SNPs in the CST complex subunit TEN1: Structural genomics approach

2018 ◽  
Author(s):  
Mohd. Amir ◽  
Vijay Kumar ◽  
Taj Mohammad ◽  
Ravins Dohare ◽  
Md. Tabish Rehman ◽  
...  
Keyword(s):  
Structural Changes ◽  
Computational Prediction ◽  
Structure Stability ◽  
Helix 12 ◽  
Functional Consequences ◽  
Non Covalent Interactions ◽  
Telomere Homeostasis ◽  
And Function ◽  
Blue Print ◽  
Covalent Interactions

TEN1 protein is a key component of CST complex, implicated in maintaining the telomere homeostasis, and provide stability to the eukaryotic genome. Mutations in TEN1 gene have higher chances of deleterious impact; thus, interpreting the number of mutations and their consequential impact on the structure, stability and function is essentially important. Here, we have investigated the structural and functional consequences of nsSNPs in the TEN1 gene. A wide array of sequence- and structure-based computational prediction tools were employed to identify the effects of 78 nsSNPs on the structure and function of TEN1 protein and deleterious nsSNPs were identified. These deleterious or destabilizing nsSNPs are scattered throughout the structure of TEN1. However, major mutations were observed in the α1-helix (12-16) and β5-strand (88-96). We further observed that mutations at C-terminal region were have higher tendency to form aggregate. In-depth structural analysis of these mutations reveals that the pathogenecity of these mutations are driven mainly through larger structural changes because of alterations in non-covalent interactions. This work provides a blue print to pinpoint the possible consequences of pathogenic mutations in the CST complex subunit TEN1.

scholarly journals Structural and functional impact of non-synonymous SNPs in the CST complex subunit TEN1: structural genomics approach

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Mohd. Amir ◽  
Vijay Kumar ◽  
Taj Mohammad ◽  
Ravins Dohare ◽  
Md. Tabish Rehman ◽  
...  
Keyword(s):  
Structural Changes ◽  
Computational Prediction ◽  
Structure Stability ◽  
Prediction Tools ◽  
Helix 12 ◽  
Functional Consequences ◽  
Non Covalent Interactions ◽  
Telomere Homeostasis ◽  
And Function ◽  
Covalent Interactions

Abstract TEN1 protein is a key component of CST complex, implicated in maintaining the telomere homeostasis, and provides stability to the eukaryotic genome. Mutations in TEN1 gene have higher chances of deleterious impact; thus, interpreting the number of mutations and their consequential impact on the structure, stability, and function is essentially important. Here, we have investigated the structural and functional consequences of nsSNPs in the TEN1 gene. A wide array of sequence- and structure-based computational prediction tools were employed to identify the effects of 78 nsSNPs on the structure and function of TEN1 protein and to identify the deleterious nsSNPs. These deleterious or destabilizing nsSNPs are scattered throughout the structure of TEN1. However, major mutations were observed in the α1-helix (12–16 residues) and β5-strand (88–96 residues). We further observed that mutations at the C-terminal region were having higher tendency to form aggregate. In-depth structural analysis of these mutations reveals that the pathogenicity of these mutations are driven mainly through larger structural changes because of alterations in non-covalent interactions. This work provides a blueprint to pinpoint the possible consequences of pathogenic mutations in the CST complex subunit TEN1.

scholarly journals On the Proton-Bound Noble Gas Dimers (Ng-H-Ng)+ and (Ng-H-Ng')+ (Ng, Ng'= He-Xe): Relationships betweenStructure, Stability, and Bonding Character

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1305
Author(s):  
Stefano Borocci ◽  
Felice Grandinetti ◽  
Nico Sanna
Keyword(s):  
Theoretical Calculations ◽  
Noble Gas ◽  
Structure Stability ◽  
Covalent Bonds ◽  
Dissociation Energies ◽  
Non Covalent Interactions ◽  
The Difference ◽  
Noble Gas Dimers ◽  
Covalent Interactions ◽  
Cluster Level

The structure, stability, and bonding character of fifteen (Ng-H-Ng)+ and (Ng-H-Ng')+ (Ng, Ng' = He-Xe) compounds were explored by theoretical calculations performed at the coupled cluster level of theory. The nature of the stabilizing interactions was, in particular, assayed using a method recently proposed by the authors to classify the chemical bonds involving the noble-gas atoms. The bond distances and dissociation energies of the investigated ions fall in rather large intervals, and follow regular periodic trends, clearly referable to the difference between the proton affinity (PA) of the various Ng and Ng'. These variations are nicely correlated with the bonding situation of the (Ng-H-Ng)+ and (Ng-H-Ng')+. The Ng-H and Ng'-H contacts range, in fact, between strong covalent bonds to weak, non-covalent interactions, and their regular variability clearly illustrates the peculiar capability of the noble gases to undergo interactions covering the entire spectrum of the chemical bond.

scholarly journals The relation between intrinsic protein conformational changes and ligand binding

2020 ◽  
Author(s):  
Marijn de Boer
Keyword(s):  
Conformational Changes ◽  
Structural Changes ◽  
Conformational Equilibrium ◽  
Biological Function ◽  
Free Protein ◽  
Classical Statistical Mechanics ◽  
Protein Conformational Changes ◽  
Ligand Free ◽  
Non Covalent Interactions ◽  
Covalent Interactions

1ABSTRACTStructural changes in proteins allow them to exist in several conformations. Non-covalent interactions with ligands drive the structural changes, thereby allowing the protein to perform its biological function. Recent findings suggest that many proteins are always in an equilibrium of different conformations and that each of these conformations can be formed by both the ligand-free and ligand-bound protein. By using classical statistical mechanics, we derived the equilibrium probabilities of forming a conformation with and without ligand. We found, under certain conditions, that increasing the probability of forming a conformation by the ligand-free protein also increases the probability of forming the same conformation when the protein has a ligand bound. Further, we found that changes in the conformational equilibrium of the ligand-free protein can increase or decrease the affinity for the ligand.

Abstract 63: Missense Mutation Lys18Asn in Dystrophin that Triggers X-Linked Cardiomyopathy Affects Protein Structure, Decreases Protein Stability and Increases Protein Unfolding

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Krishna Mallela ◽  
Surinder Singh ◽  
Geoffrey Armstrong
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Structural Changes ◽  
Molecular Mechanisms ◽  
Actin Binding ◽  
Structure Stability ◽  
Functional Protein ◽  
Mutation Site ◽  
Relative Population ◽  
And Function

A genetic mutation in dystrophin that replaces lysine at amino acid position 18 by an asparagine (K18N) results in X-linked cardiomyopathy (XCM), however, the underlying molecular mechanisms are not known. Such knowledge might help in developing effective therapies to treat XCM. The first step in understanding disease-triggering mechanisms is to probe how mutation affects protein structure and function. The K18N mutation occurs in the N-terminal actin binding domain (N-ABD) of dystrophin. Here, we examined the effect of K18N on the structure, stability, and function of N-ABD. Fig. 1A shows the 15 N- 1 H HSQC NMR spectrum before and after the mutation. Each crosspeak in the spectrum represents the structure around an amino acid. Mutation affects the position of nearly all the crosspeaks. These changes are not just located at the mutation site, but were observed in regions far away from the mutation site and also in the three actin binding regions with which N-ABD interacts with actin. In addition, the mutation makes the protein more dynamic. These structural changes result in decreased actin binding function of N-ABD. Also, the K18N mutation decreases the stability by ΔΔG = 5.3 kcal/mol (Fig. 1B) and increases the rate of unfolding by 3.2 times (Fig. 1C), which exponentially increase the relative population of unfolded state that is more prone to proteolysis and hence will result in decreased levels of the functional protein. These results indicate that the physical mechanism by which the K18N mutation triggers the disease might be by affecting protein structure leading to decreased actin binding and by decreasing the net protein levels leading to decreased net function.

scholarly journals A pedagogical view about the design of isoxazolyl-penicillins of the ampc betalactamase receptor 1fcm using the docking molecular technique

2021 ◽  
Vol 10 (9) ◽  
pp. 121-137
Author(s):  
Laura Alejandra Heredia Parra ◽  
Edson Armando Vigoya Ovalle ◽  
Astrid Ramírez Valencia ◽  
Luis Eduardo Peña Prieto
Keyword(s):  
Amino Acids ◽  
Structural Changes ◽  
Reference Value ◽  
Data Bank ◽  
Molecular Technique ◽  
Non Covalent Interactions ◽  
New Interactions ◽  
Covalent Interactions ◽  
Pharmacophore Group ◽  
Selection Of

The present work mainly exposes the result of the search for molecules, derived from the structural changes of the drug Cloxacillin in its phenyl radical, which is chlorinated, likewise, the selection of the pharmacophore group is evidenced, which allowed to specify the aforementioned objective. Secondly, the selected target was beta-lactamase, with 1FCM nomenclature, registered in the database, Protein Data Bank, in the same way, the amino acids involved in non-covalent interactions are found, in this order of ideas, they were raised, 22 molecules that presented an affinity energy lower than -8.0 Kcal/mol, this data stated above, will become the reference value, to postulate 6 molecules that have registered a lower affinity, generated by the Autodock Vina software. To conclude, the structural optimization of the leading drug is given as a result, together with its new interactions in the amino acids LYS64, ASN149, THR313 and SER61.

Digestibility and supramolecular structural changes of maize starch by non-covalent interactions with gallic acid

2017 ◽  
Vol 8 (2) ◽  
pp. 720-730 ◽  
Author(s):  
Chengdeng Chi ◽  
Xiaoxi Li ◽  
Yiping Zhang ◽  
Ling Chen ◽  
Lin Li ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Gallic Acid ◽  
Structural Changes ◽  
Maize Starch ◽  
Enzymatic Digestibility ◽  
Multi Scale ◽  
Non Covalent Interactions ◽  
Scale Structures ◽  
Covalent Interactions

The synergistic effect of starch–GA complexes with more ordered multi-scale structures and the released GA inhibition decrease starch enzymatic digestibility.

scholarly journals Concerning the Role of σ-Hole in Non-Covalent Interactions: Insights from the Study of the Complexes of ArBeO with Simple Ligands

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4477
Author(s):  
Stefano Borocci ◽  
Felice Grandinetti ◽  
Nico Sanna
Keyword(s):  
Molecular Electrostatic Potential ◽  
Noble Gas ◽  
Coupled Cluster ◽  
Structure Stability ◽  
Chemical Bonds ◽  
Cluster Calculations ◽  
Non Covalent Interactions ◽  
Covalent Interactions ◽  
Coupled Cluster Calculations

The structure, stability, and bonding character of some exemplary LAr and L-ArBeO (L = He, Ne, Ar, N2, CO, F2, Cl2, ClF, HF, HCl, NH3) were investigated by MP2 and coupled-cluster calculations, and by symmetry-adapted perturbation theory. The nature of the stabilizing interactions was also assayed by the method recently proposed by the authors to classify the chemical bonds in noble-gas compounds. The comparative analysis of the LAr and L-ArBeOunraveled geometric and bonding effects peculiarly related to the σ-hole at the Ar atom of ArBeO, including the major stabilizing/destabilizing role of the electrostatic interactionensuing from the negative/positive molecular electrostatic potential of L at the contact zone with ArBeO. The role of the inductive and dispersive components was also assayed, making itpossible to discernthe factors governing the transition from the (mainly) dispersive domain of the LAr, to the σ-hole domain of the L-ArBeO. Our conclusions could be valid for various types of non-covalent interactions, especially those involving σ-holes of respectable strength such as thoseoccurring in ArBeO.

NON COVALENT INTERACTIONS IN LARGE DIAMONDOID DIMERS IN THE GAS PHASE - A MICROWAVE STUDY

2017 ◽  
Author(s):  
Cristobal Perez ◽  
Melanie Schnell ◽  
Peter Schreiner ◽  
Norbert Mitzel ◽  
Yury Vishnevskiy ◽  
...  
Keyword(s):  
Gas Phase ◽  
Non Covalent Interactions ◽  
Covalent Interactions
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