scholarly journals A Missense Mutation (R723H) in the Head Motor Domain of β-MYH7 gene in an Indian HCM Patient and Phenotypic Plasticity

2021 ◽  
Vol 4 (17) ◽  
pp. 01-07
Author(s):  
Deepa Selvi Rani ◽  
Gnana Veera Subhashini ◽  
Ambure Sharadhadevi ◽  
Emmanuel Cyril ◽  
Kumarasamy Thangaraj
Keyword(s):  
Missense Mutation ◽  
Protein Structures ◽  
3D Structure ◽  
Homology Model ◽  
Motor Domain ◽  
Mutation Site ◽  
Bioinformatic Tools ◽  
Evolutionarily Conserved ◽  
Non Covalent Interactions ◽  
Covalent Interactions

Mutations in the β-MYH7 gene are one of the major causes that lead to cardiomyopathies. However, to differentiate a causative nsSNP and its impact on protein structure remains a major challenge. In the present study, we detected a missense mutation Arg723His in the head motor domain of β-MYH7 in a HCM patient, and it was absent in 207 healthy individuals. The mutant (R723H) has been found to alter an evolutionarily conserved amino acid. In addition, the mutant (R723H) was predicted pathogenic by Polyphen-2 and SIFT bioinformatic tools. Further, the superimposed 3D structure of the mutant (p.His723 homology model) with native (p. Arg723) displayed the root means square deviation (RMSD) of ~3.38A0. We know that the non-covalent interactions such as hydrophobic, electrostatic, Van der Waals, and hydrogen bonds between amino acids are at the heart of stabilizing protein structures. Here, we demonstrated how the mutant (p.His723) has disrupted a critical non-covalent interactions network at the mutation site and may contribute to the disease phenotype. Hence, our findings in the future could pave the way for developing small molecular modulators or myosin-targeted therapies for heart failure.

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.

Interaction of Platinum-based Drugs with Proteins: An Overview of Representative Crystallographic Studies

2020 ◽  
Vol 20 ◽  
Author(s):  
Giarita Ferraro ◽  
Domenico Loreto ◽  
Antonello Merlino
Keyword(s):  
Molecular Mechanisms ◽  
Protein Structures ◽  
Molecular Structures ◽  
X Ray Diffraction ◽  
Metal Compounds ◽  
X Ray ◽  
Metal Ligands ◽  
Protein Adduct ◽  
Non Covalent Interactions ◽  
Covalent Interactions

: Pt-based drugs are widely used in clinics for the treatment of cancer. The mechanism of action of these molecules rely on their interaction with DNA. However, the recognition of these metal compounds by proteins plays an important role in defining pharmacokinetics, side effects and their overall pharmacological profiles. Single crystal X-ray diffraction studies provided important information on the molecular mechanisms at the basis of this process. Here, the molecular structures of representative adducts obtained upon reaction with proteins of selected Pt-based drugs, including cisplatin, carboplatin and oxaliplatin, were briefly described and comparatively examined. Data indicate that metal ligands play a significant role in driving the reaction of Pt compounds with proteins; non-covalent interactions that are formed in the early steps of Pt compound/protein recognition process play a crucial role in defining the structure of the final Pt-protein adduct. In the metalated protein structures, Pt centers coordinate few protein side chains, such as His, Met, Cys, Asp, Glu and Lys residues upon releasing of labile ligands.

scholarly journals Clustering of Aromatic Amino Acid Residues around Methionine in Proteins

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 6
Author(s):  
Curtis A. Gibbs ◽  
David S. Weber ◽  
Jeffrey J. Warren
Keyword(s):  
Amino Acid ◽  
Aromatic Amino Acid ◽  
Protein Structures ◽  
Amino Acid Residues ◽  
Aromatic Rings ◽  
Aromatic Residues ◽  
Sequence Identity ◽  
Protein Functions ◽  
Non Covalent Interactions ◽  
Covalent Interactions

Short-range, non-covalent interactions between amino acid residues determine protein structures and contribute to protein functions in diverse ways. The interactions of the thioether of methionine with the aromatic rings of tyrosine, tryptophan, and/or phenylalanine has long been discussed and such interactions are favorable on the order of 1–3 kcal mol−1. Here, we carry out a new bioinformatics survey of known protein structures where we assay the propensity of three aromatic residues to localize around the [-CH2-S-CH3] of methionine. We term these groups “3-bridge clusters”. A dataset consisting of 33,819 proteins with less than 90% sequence identity was analyzed and such clusters were found in 4093 structures (or 12% of the non-redundant dataset). All sub-classes of enzymes were represented. A 3D coordinate analysis shows that most aromatic groups localize near the CH2 and CH3 of methionine. Quantum chemical calculations support that the 3-bridge clusters involve a network of interactions that involve the Met-S, Met-CH2, Met-CH3, and the π systems of nearby aromatic amino acid residues. Selected examples of proposed functions of 3-bridge clusters are discussed.

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>

scholarly journals Heterogenisation of polyoxometalates and other metal-based complexes in metal–organic frameworks: from synthesis to characterisation and applications in catalysis

2021 ◽  
Author(s):  
P. Mialane ◽  
C. Mellot-Draznieks ◽  
P. Gairola ◽  
M. Duguet ◽  
Y. Benseghir ◽  
...  
Keyword(s):  
Metal Organic Frameworks ◽  
Coordination Complexes ◽  
Metal Organic ◽  
Non Covalent Interactions ◽  
Molecular Catalysts ◽  
Covalent Interactions

This review provides a thorough overview of composites with molecular catalysts (polyoxometalates, or organometallic or coordination complexes) immobilised into MOFs via non-covalent interactions.

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