scholarly journals Effect of Abolition of Intersubunit Salt Bridges on Allosteric Protein Structural Dynamics

2021 ◽  
Author(s):  
Hyotcherl Ihee ◽  
Minseo Choi ◽  
Jong Goo Kim ◽  
Srinivasan Muniyappan ◽  
Hanui Kim ◽  
...  
Keyword(s):  
Structural Dynamics ◽  
Protein Function ◽  
Crucial Role ◽  
Salt Bridge ◽  
Structural Factors ◽  
Salt Bridges ◽  
Protein Structural Dynamics ◽  
Non Covalent Interactions ◽  
Covalent Interactions ◽  
Allosteric Protein

Salt bridge, one of the representative structural factors established by non-covalent interactions, plays a crucial role in stabilizing the structure and regulating the protein function, but its role in dynamic...

scholarly journals RIP-MD: a tool to study residue interaction networks in protein molecular dynamics

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5998 ◽  
Author(s):  
Sebastián Contreras-Riquelme ◽  
Jose-Antonio Garate ◽  
Tomas Perez-Acle ◽  
Alberto J.M. Martin
Keyword(s):  
Molecular Dynamics ◽  
Protein Structures ◽  
Md Simulations ◽  
Relevant Information ◽  
Interaction Networks ◽  
Salt Bridges ◽  
Residue Interaction ◽  
Non Covalent Interactions ◽  
Protein Molecular Dynamics ◽  
Covalent Interactions

Protein structure is not static; residues undergo conformational rearrangements and, in doing so, create, stabilize or break non-covalent interactions. Molecular dynamics (MD) is a technique used to simulate these movements with atomic resolution. However, given the data-intensive nature of the technique, gathering relevant information from MD simulations is a complex and time consuming process requiring several computational tools to perform these analyses. Among different approaches, the study of residue interaction networks (RINs) has proven to facilitate the study of protein structures. In a RIN, nodes represent amino-acid residues and the connections between them depict non-covalent interactions. Here, we describe residue interaction networks in protein molecular dynamics (RIP-MD), a visual molecular dynamics (VMD) plugin to facilitate the study of RINs using trajectories obtained from MD simulations of proteins. Our software generates RINs from MD trajectory files. The non-covalent interactions defined by RIP-MD include H-bonds, salt bridges, VdWs, cation-π, π–π, Arginine–Arginine, and Coulomb interactions. In addition, RIP-MD also computes interactions based on distances between Cαs and disulfide bridges. The results of the analysis are shown in an user friendly interface. Moreover, the user can take advantage of the VMD visualization capacities, whereby through some effortless steps, it is possible to select and visualize interactions described for a single, several or all residues in a MD trajectory. Network and descriptive table files are also generated, allowing their further study in other specialized platforms. Our method was written in python in a parallelized fashion. This characteristic allows the analysis of large systems impossible to handle otherwise. RIP-MD is available at http://www.dlab.cl/ripmd.

Crystallography based investigation of weak interaction for drug designing against COVID-19

2021 ◽  
Author(s):  
Nayim Sepay ◽  
Pranab C. Saha ◽  
Zarrin Shahzadi ◽  
Aratrika Chakraborty ◽  
Umesh Chandra Halder
Keyword(s):  
Small Molecules ◽  
Weak Interaction ◽  
Protein Function ◽  
Complete Understanding ◽  
Drug Designing ◽  
Non Covalent Interactions ◽  
Covalent Interactions

Interactions between protein-small molecules plays an important roles in inhibition of protein function. However, lack of proper knowledge of non-covalent interactions acts as a barrier towards complete understanding of factors...

scholarly journals Comparative physicochemical and evolutionary study of SARS-CoV-2 and SARS with special reference to salt bridge and their microenvironment: A plausible explanation for divergency, stability and severity of SARS-CoV-2

2020 ◽  
Author(s):  
Debanjan Mitra ◽  
Aditya K. Pal ◽  
Pradeep Kumar Das Mohapatra
Keyword(s):  
Crucial Role ◽  
Protein Sequences ◽  
Salt Bridge ◽  
Extreme Conditions ◽  
Salt Bridges ◽  
Wuhan City ◽  
High Energies ◽  
The World ◽  
Charged Residues ◽  
Short Time

Abstract The occurrence of concentrated pneumonia cases in Wuhan city, Hubei province of China was first reported on December 30, 2019. Currently, it is known as COVID 19 and now it is a nightmare for the whole world. SARS CoV first reported in 2002, but not spread worldwide. After 18 years, in 2020 it reappears and spread worldwide as SARS-CoV-2 (COVID 19), the most dangerous virus creating disease in the world. Is it possible to create a favorable evolution within this short time? If possible, then what are those properties that are changed in SARS-CoV-2 to make it undefeated? What are the basic differences between SARS-CoV-2 and SARS? This study will find all those queries. Here, all protein sequences of SARS-CoV-2 and SARS are retrieved from the database to check their physicochemical, evolutionary and structural properties. Results showed that, charged residues are playing a key role in SARS-CoV-2 evolution. SARS-CoV-2 increases its polarity by the help of charged residues, not by the polar residues. Their divergence is also strictly restricted. Induction of salt bridges with their high energies makes it very stable in any extreme conditions. Microenvironment residues also play a very crucial role in its stability. Mostly residues are favorable and contribute high energies. These microenvironment residues help in protein engineering to reduce its stability and make them week. This comparative study will help to understand the evolution from SARS to SARS-CoV-2.

scholarly journals Functional Implications of Disordered Terminal Regions of Macrotyloma uniflorum Bowman-Birk Inhibitors: A Molecular Dynamics Study

2017 ◽  
Author(s):  
Abhishek Acharya
Keyword(s):  
Protein Function ◽  
Hot Spot ◽  
Computational Simulation ◽  
Experimental Studies ◽  
Salt Bridge ◽  
Conformational Ensemble ◽  
Salt Bridges ◽  
Exchange Method ◽  
Hamiltonian Replica Exchange ◽  
Intrinsically Disordered

AbstractBowman-Birk Inhibitors (BBI) – a class of serine protease inhibitors is of considerable interest due to their anti-inflammatory and anti-carcinogenic properties. Recent efforts have focused on understanding the structure and dynamics of these inhibitors, and the molecular mechanism behind its bioactive properties. BBI derived from Horsegram seeds is an interesting member of the class that exists as a number of isoforms that differ in length at the C- and N-terminal disordered regions. Interestingly, the length (or conversely, truncation) of the terminal regions affect whether the protein exists as a dimer or monomer. Here, we have investigated the mechanism of dimerization in Horsegram BBI. A recent study has proposed that the dimerization occur via a C-terminal hook that forms a salt bridge with the opposite monomer and is pivotal to the dimerization process. We have employed long computational simulation methods to predict the stability of the proposed C-terminal hook; we show that the terminal regions are highly disordered and the salt bridges are significantly solvent exposed. Further, using Hamiltonian replica exchange method, we have sought to obtain the conformational ensemble of the disordered terminal regions and have identified a conformational state that provides an interaction hot-spot that aids in the dimerization of HGI. Our analysis predicts an alternate model of dimerization that largely agrees with previous experimental studies and yet again, highlights the importance of intrinsically disordered region in tailoring the protein function.

scholarly journals An Oncometabolite Isomer Rapidly Induces A Pathophysiological Protein Modification

2020 ◽  
Author(s):  
Sarah E. Bergholtz ◽  
Chloe A. Briney ◽  
Susana S. Najera ◽  
Minervo Perez ◽  
W. Marston Linehan ◽  
...  
Keyword(s):  
Protein Function ◽  
Protein Modification ◽  
Living Cells ◽  
Cellular Assays ◽  
Non Covalent Interactions ◽  
Regulate Protein ◽  
Chemical Strategy ◽  
Covalent Interactions

ABSTRACTMetabolites regulate protein function via covalent and non-covalent interactions. However, manipulating these interactions in living cells remains a major challenge. Here we report a chemical strategy for inducing cysteine S-succination, a non-enzymatic posttranslational modification derived from the oncometabolite fumarate. Using a combination of antibody-based detection and kinetic assays we benchmark the in vitro and cellular reactivity of two novel S-succination “agonists,” maleate and 2-bromosuccinate. Cellular assays reveal maleate to be a more potent and less toxic inducer of S-succination which can activate KEAP1-NRF2 signaling in living cells. By enabling the cellular reconstitution of an oncometabolite-protein interaction with physiochemical accuracy and minimal toxicity, this study provides a methodological basis for better understanding the signaling role of metabolites in disease.

scholarly journals NEDD8 Deamidation Inhibits Cullin RING Ligase Dynamics

2021 ◽  
Vol 12 ◽  
Author(s):  
Priyesh Mohanty ◽  
Kiran Sankar Chatterjee ◽  
Ranabir Das
Keyword(s):  
Conformational Changes ◽  
Salt Bridge ◽  
Md Simulations ◽  
Enteric Bacteria ◽  
Covalent Attachment ◽  
E3 Ligases ◽  
Ring E3 Ligase ◽  
Non Covalent Interactions ◽  
Ring E3 ◽  
Covalent Interactions

Cullin-RING ligases (CRLs) are a significant subset of Ubiquitin E3 ligases that regulate multiple cellular substrates involved in innate immunity, cytoskeleton modeling, and cell cycle. The glutamine deamidase Cycle inhibitory factor (Cif) from enteric bacteria inactivates CRLs to modulate these processes in the host cell. The covalent attachment of a Ubiquitin-like protein NEDD8 catalytically activates CRLs by driving conformational changes in the Cullin C-terminal domain (CTD). NEDDylation results in a shift from a compact to an open CTD conformation through non-covalent interactions between NEDD8 and the WHB subdomain of CTD, eliminating the latter’s inhibitory interactions with the RING E3 ligase-Rbx1/2. It is unknown whether the non-covalent interactions are sufficient to stabilize Cullin CTD’s catalytic conformation. We studied the dynamics of Cullin-CTD in the presence and absence of NEDD8 using atomistic molecular dynamics (MD) simulations. We uncovered that NEDD8 engages in non-covalent interactions with 4HB/αβ subdomains in Cullin-CTD to promote open conformations. Cif deamidates glutamine 40 in NEDD8 to inhibit the conformational change in CRLs by an unknown mechanism. We investigated the effect of glutamine deamidation on NEDD8 and its interaction with the WHB subdomain post-NEDDylation using MD simulations and NMR spectroscopy. Our results suggest that deamidation creates a new intramolecular salt bridge in NEDD8 to destabilize the NEDD8/WHB complex and reduce CRL activity.

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

Vapour Pressure Isotope Effect on Evaporation from Pure Organic Phases - a PIMD Approach

2020 ◽  
Author(s):  
Luis Vasquez ◽  
Agnieszka Dybala-Defratyka
Keyword(s):  
Path Integral ◽  
Vapour Pressure ◽  
Density Functional ◽  
Isotope Effects ◽  
Tight Binding ◽  
Decomposition Analysis ◽  
Energy Decomposition Analysis ◽  
Special Importance ◽  
Non Covalent Interactions ◽  
Covalent Interactions

<p></p><p>Very often in order to understand physical and chemical processes taking place among several phases fractionation of naturally abundant isotopes is monitored. Its measurement can be accompanied by theoretical determination to provide a more insightful interpretation of observed phenomena. Predictions are challenging due to the complexity of the effects involved in fractionation such as solvent effects and non-covalent interactions governing the behavior of the system which results in the necessity of using large models of those systems. This is sometimes a bottleneck and limits the theoretical description to only a few methods.<br> In this work vapour pressure isotope effects on evaporation from various organic solvents (ethanol, bromobenzene, dibromomethane, and trichloromethane) in the pure phase are estimated by combining force field or self-consistent charge density-functional tight-binding (SCC-DFTB) atomistic simulations with path integral principle. Furthermore, the recently developed Suzuki-Chin path integral is tested. In general, isotope effects are predicted qualitatively for most of the cases, however, the distinction between position-specific isotope effects observed for ethanol was only reproduced by SCC-DFTB, which indicates the importance of using non-harmonic bond approximations.<br> Energy decomposition analysis performed using the symmetry-adapted perturbation theory (SAPT) revealed sometimes quite substantial differences in interaction energy depending on whether the studied system was treated classically or quantum mechanically. Those observed differences might be the source of different magnitudes of isotope effects predicted using these two different levels of theory which is of special importance for the systems governed by non-covalent interactions.</p><br><p></p>

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