scholarly journals Chiral Recognition of Dansyl Derivatives with an Amino Acid-Based Molecular Micelle: A Molecular Dynamics Investigation

2021 ◽  
Vol 11 (02) ◽  
pp. 64-86
Author(s):  
Mauro Garcia ◽  
Nathan Black ◽  
Eugene Billiot ◽  
Fereshteh Billiot ◽  
Kevin F. Morris ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Chiral Recognition ◽  
Dansyl Derivatives

scholarly journals Chiral recognition of dansyl-derivatives by amino acid-based molecular micelles using molecular dynamics simulations

2021 ◽  
Author(s):  
Mauro Garcia ◽  
Nathan Black ◽  
Eugene Billiot ◽  
Fereshteh Billiot ◽  
Yayin Fang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Molecular Dynamics Simulations ◽  
Chiral Recognition ◽  
Dansyl Derivatives ◽  
Dynamics Simulations

scholarly journals Chiral recognition of dansyl-derivatives by amino acid-based molecular micelles using molecular dynamics simulations

2021 ◽  
Author(s):  
Mauro Garcia ◽  
Nathan Black ◽  
Eugene Billiot ◽  
Fereshteh Billiot ◽  
Yayin Fang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Molecular Dynamics Simulations ◽  
Chiral Recognition ◽  
Dansyl Derivatives ◽  
Dynamics Simulations

Using molecular dynamics simulations to identify the key factors responsible for chiral recognition by an amino acid-based molecular micelle

2018 ◽  
Vol 40 (5) ◽  
pp. 716-727 ◽  
Author(s):  
Kevin F. Morris ◽  
Eugene J. Billiot ◽  
Fereshteh H. Billiot ◽  
Jordan A. Ingle ◽  
Kevin B. Krause ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Molecular Dynamics Simulations ◽  
Chiral Recognition ◽  
Key Factors ◽  
Dynamics Simulations

Schistosomal Sulfotransferase Interaction with Oxamniquine Involves Hybrid Mechanism of Induced-fit and Conformational Selection

2020 ◽  
Vol 16 (4) ◽  
pp. 451-459 ◽  
Author(s):  
Fortunatus C. Ezebuo ◽  
Ikemefuna C. Uzochukwu
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Binding Energy ◽  
Binding Site ◽  
Conformational Dynamics ◽  
Side Chain ◽  
Amino Acid Residues ◽  
Conformational Selection ◽  
Hybrid Mechanism ◽  
Dynamics Simulations

Background: Sulfotransferase family comprises key enzymes involved in drug metabolism. Oxamniquine is a pro-drug converted into its active form by schistosomal sulfotransferase. The conformational dynamics of side-chain amino acid residues at the binding site of schistosomal sulfotransferase towards activation of oxamniquine has not received attention. Objective: The study investigated the conformational dynamics of binding site residues in free and oxamniquine bound schistosomal sulfotransferase systems and their contribution to the mechanism of oxamniquine activation by schistosomal sulfotransferase using molecular dynamics simulations and binding energy calculations. Methods: Schistosomal sulfotransferase was obtained from Protein Data Bank and both the free and oxamniquine bound forms were subjected to molecular dynamics simulations using GROMACS-4.5.5 after modeling it’s missing amino acid residues with SWISS-MODEL. Amino acid residues at its binding site for oxamniquine was determined and used for Principal Component Analysis and calculations of side-chain dihedrals. In addition, binding energy of the oxamniquine bound system was calculated using g_MMPBSA. Results: The results showed that binding site amino acid residues in free and oxamniquine bound sulfotransferase sampled different conformational space involving several rotameric states. Importantly, Phe45, Ile145 and Leu241 generated newly induced conformations, whereas Phe41 exhibited shift in equilibrium of its conformational distribution. In addition, the result showed binding energy of -130.091 ± 8.800 KJ/mol and Phe45 contributed -9.8576 KJ/mol. Conclusion: The results showed that schistosomal sulfotransferase binds oxamniquine by relying on hybrid mechanism of induced fit and conformational selection models. The findings offer new insight into sulfotransferase engineering and design of new drugs that target sulfotransferase.

scholarly journals New CHARMM force field parameters for dehydrated amino acid residues, the key to lantibiotic molecular dynamics simulations

RSC Advances ◽  
2014 ◽  
Vol 4 (89) ◽  
pp. 48621-48631 ◽  
Author(s):  
Eleanor R. Turpin ◽  
Sam Mulholland ◽  
Andrew M. Teale ◽  
Boyan B. Bonev ◽  
Jonathan D. Hirst
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Force Field ◽  
Molecular Dynamics Simulations ◽  
Amino Acid Residues ◽  
Charmm Force Field ◽  
Force Field Parameters ◽  
Dynamics Simulations

Chiral recognition of amino acid derivatives by 1,1′-binaphthalene-8,8′-diol

1996 ◽  
Vol 37 (24) ◽  
pp. 4153-4156 ◽  
Author(s):  
Takeo Kawabata ◽  
Akio Kuroda ◽  
Eizo Nakata ◽  
Kiyosei Takasu ◽  
Kaoru Fuji
Keyword(s):  
Amino Acid ◽  
Chiral Recognition ◽  
Amino Acid Derivatives

ReaxFF-based molecular dynamics simulation of the interaction between plasma ROS and the receptor-binding domain of the spike protein in the capsid protein of SARS-CoV-2

2021 ◽  
Author(s):  
Huichao Wang ◽  
Tong Zhao ◽  
Shuhui Yang ◽  
Liang Zou ◽  
Xiaolong Wang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Amino Acid ◽  
Capsid Protein ◽  
Receptor Binding ◽  
Hydrogen Abstraction ◽  
Binding Domain ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Amino Acid Residues ◽  
Global Epidemic

Abstract Under the severe situation of the current global epidemic, researchers have been working hard to find a reliable way to suppress the infection of the virus and prevent the spread of the epidemic. Studies have shown that the recognition and binding of human angiotensin-converting enzyme 2 (ACE2) by the receptor-binding domain (BRD) of spike protein on the surface of SARS-CoV-2 is a crucial step for SARS-CoV-2 to invade human receptor cells, and blocking this process can inhibit the virus from invading human normal cells. Plasma treatment can disrupt the structure of the RBD and effectively block the binding process. However, the mechanism by which plasma blocks the recognition and binding between the two is not clear. In this study, reaction process between reactive oxygen species (ROS) in plasma and the molecular model of RBD was simulated using a reactive molecular dynamics method. The results showed that the destruction of RBD molecule by ROS was triggered by hydrogen abstraction reactions. O and OH abstracted H atoms from RBD, while the H atoms of H2O2 and HO2 were abstracted by RBD. The hydrogen abstraction resulted in the breakage of C-H, N-H, O-H and C=O bonds and the formation of C=C, C=N bonds. The addition reaction of OH increased the number of O-H bonds and caused the formation of C-O, N-O and O-H bonds. The dissociation of N-H bonds led to the destruction of the original structure of peptide bonds and amino acid residues, change the type of amino acid residues, and caused the conversion of N-C and N=C, C=O and C-O. The simulation partially elucidated the microscopic mechanism of the interaction between ROS in plasma and the capsid protein of SARS-CoV-2, providing theoretical support for the control of SARS-CoV-2 infection by plasma, a contribution to overcoming the global epidemic problem.

scholarly journals Structural and Functional Consequences of Age-Related Isomerization in α-Crystallins

2018 ◽  
Author(s):  
Yana A. Lyon ◽  
Dylan L. Riggs ◽  
Miranda P. Collier ◽  
Matteo T. Degiacomi ◽  
Justin L.P. Benesch ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Molecular Dynamics ◽  
Amino Acid ◽  
Native Mass Spectrometry ◽  
Salt Bridges ◽  
Loss Of Function ◽  
Post Translational Modification ◽  
Age Related ◽  
Αb Crystallin ◽  
Functional Consequences

AbstractLong-lived proteins are subject to spontaneous degradation and may accumulate a range of modifications over time, including subtle alterations such as isomerization. Recently, tandem-mass spectrometry approaches have enabled the identification and detailed characterization of such peptide isomers, including those differing only in chirality. However, the structural and functional consequences of these perturbations remain largely unexplored. Here we examine the site-specific impact of isomerization of aspartic acid and epimerization of serine in human αA- and αB-crystallin. From a total of 81 sites of modification identified in aged eye lenses, four (αBSer59, αASer162, αBAsp62, αBAsp109) map to crucial oligomeric interfaces. To characterize the effect of isomerization on quaternary assembly, molecular dynamics calculations and native mass spectrometry experiments were performed on recombinant forms of αA- and αB-crystallin that incorporate, or mimic, isomerized residues. In all cases, oligomerization is significantly affected, with epimerization of a single serine residue (αASer162) sufficing to weaken inter-subunit binding dramatically. Furthermore, phosphorylation of αBSer59, known to play an important regulatory role in oligomerization, is severely inhibited by serine epimerization and altered by isomerization of nearby αBAsp62. Similarly, isomerization of αBAsp109 disrupts a vital salt-bridge with αBArg120, a loss previously shown to yield aberrant oligomerization and aggregation in several disease variants. Our results illustrate how isomerization of amino-acid residues, which may seem like a minor structural perturbation, can have profound consequences on protein assembly and activity by disrupting specific hydrogen bonds and salt bridges.Significance StatementProteins play numerous critical roles in our bodies but suffer damage with increasing age. For example, isomerization is a spontaneous post-translational modification that alters the three-dimensional connectivity of an amino acid, yet remains invisible to traditional proteomic experiments. Herein, radical-based fragmentation was used for isomer identification while molecular dynamics and native mass spectrometry were utilized to assess structural consequences. The results demonstrate that isomerization disrupts both oligomeric assembly and phosphorylation in the α-crystallins, which are long-lived proteins in the lens of the eye. The loss of function associated with these modifications is likely connected to age-related diseases such as cataract and neurodegenerative disorders, while the methodologies we present represent a framework for structure-function studies on other isomerized proteins.

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