Conformational transitions in the Ramachandran space of amino acids using the dynamic rotational isomeric state (DRIS) model

2014 ◽  
Vol 10 (3) ◽  
pp. 663-671 ◽  
Author(s):  
Cigdem Sevim Bayrak ◽  
Burak Erman
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Isomeric State ◽  
Md Simulations ◽  
Conformational Transitions ◽  
Computational Method ◽  
Local Dynamics ◽  
Rotational Isomeric State ◽  
Rotational Transitions ◽  
Isomeric States

We present a computational method to investigate conformational transitions of the twenty amino acids based on molecular dynamics (MD) simulations and the dynamic rotational isomeric state (DRIS) model. Local dynamics of twenty amino acids resulting from rotational transitions between isomeric states are analyzed.

scholarly journals On the Use of the Discrete Constant pH Molecular Dynamics to Describe the Conformational Space of Peptides

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 99
Author(s):  
Cristian Privat ◽  
Sergio Madurga ◽  
Francesc Mas ◽  
Jaime Rubio-Martínez
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Md Simulations ◽  
Point Of View ◽  
Conformational Space ◽  
Conformational Sampling ◽  
Protonation State ◽  
Constant Ph ◽  
Biochemical Systems ◽  
Constant Ph Molecular Dynamics

Solvent pH is an important property that defines the protonation state of the amino acids and, therefore, modulates the interactions and the conformational space of the biochemical systems. Generally, this thermodynamic variable is poorly considered in Molecular Dynamics (MD) simulations. Fortunately, this lack has been overcome by means of the Constant pH Molecular Dynamics (CPHMD) methods in the recent decades. Several studies have reported promising results from these approaches that include pH in simulations but focus on the prediction of the effective pKa of the amino acids. In this work, we want to shed some light on the CPHMD method and its implementation in the AMBER suitcase from a conformational point of view. To achieve this goal, we performed CPHMD and conventional MD (CMD) simulations of six protonatable amino acids in a blocked tripeptide structure to compare the conformational sampling and energy distributions of both methods. The results reveal strengths and weaknesses of the CPHMD method in the implementation of AMBER18 version. The change of the protonation state according to the chemical environment is presumably an improvement in the accuracy of the simulations. However, the simulations of the deprotonated forms are not consistent, which is related to an inaccurate assignment of the partial charges of the backbone atoms in the CPHMD residues. Therefore, we recommend the CPHMD methods of AMBER program but pointing out the need to compare structural properties with experimental data to bring reliability to the conformational sampling of the simulations.

Molecular dynamics simulations on the effects of carbon nanotubes on mechanical properties of bisphenol E cyanate ester validating experimental results

2016 ◽  
Vol 36 (3) ◽  
pp. 186-195 ◽  
Author(s):  
P Subba Rao ◽  
K Renji ◽  
MR Bhat
Keyword(s):  
Mechanical Properties ◽  
Carbon Nanotubes ◽  
Molecular Dynamics ◽  
Experimental Studies ◽  
Md Simulations ◽  
Geometric Optimization ◽  
Cyanate Ester ◽  
Computational Method ◽  
Interfacial Region ◽  
Atomistic Models

This paper presents molecular dynamics (MD) simulations on the effects of carbon nanotubes (CNTs) without and with chemical functionalization, on the mechanical properties of bisphenol E cyanate ester (BECy) – a potential structural resin. Atomistic models of CNTs, functionalized CNTs (fCNTs), BECy resin, CNT-BECy and fCNT-BECy resins with definite quantity of CNT/fCNT are built. Using these atomistic models, mechanical properties of the above nanosystems are estimated through a computational method involving geometric optimization and equilibration through MD by judiciously establishing various parameters. Adoptability of the approach taken up in this work to model and solve complex nanosystems capturing interactions in the interfacial region between CNT/fCNT and the resin to understand the mechanical behaviour has been highlighted. These investigations have yielded interesting and encouraging results to arrive at optimum quantity of CNTs/fCNTs to be added to achieve enhanced mechanical properties of BECy resin that validate the previous experimental studies carried out by the authors infusing similar quantities of CNTs and fCNTs into BECy.

scholarly journals Molecular dynamics simulations of charged and neutral lipid bilayers: treatment of electrostatic interactions.

2003 ◽  
Vol 50 (3) ◽  
pp. 789-798 ◽  
Author(s):  
Tomasz Róg ◽  
Krzysztof Murzyn ◽  
Marta Pasenkiewicz-Gierula
Keyword(s):  
Experimental Data ◽  
Molecular Dynamics ◽  
Lipid Bilayers ◽  
Long Range ◽  
Electrostatic Interactions ◽  
Md Simulations ◽  
Computational Method ◽  
Simulation Protocol ◽  
Speed Up ◽  
Dynamics Simulations

Molecular dynamics (MD) simulations complement experimental methods in studies of the structure and dynamics of lipid bilayers. The choice of algorithms employed in this computational method represents a trade-off between the accuracy and real calculation time. The largest portion of the simulation time is devoted to calculation of long-range electrostatic interactions. To speed-up evaluation of these interactions, various approximations have been used. The most common ones are the truncation of long-range interactions with the use of cut-offs, and the particle-mesh Ewald (PME) method. In this study, several multi-nanosecond cut-off and PME simulations were performed to establish the influence of the simulation protocol on the bilayer properties. Two bilayers were used. One consisted of neutral phosphatidylcholine molecules. The other was a mixed lipid bilayer consisting of neutral phosphatidylethanolamine and negatively charged phosphatidylglycerol molecules. The study shows that the cut-off simulation of a bilayer containing charge molecules generates artefacts; in particular the mobility and order of the charged molecules are vastly different from those determined experimentally. In the PME simulation, the bilayer properties are in general agreement with experimental data. The cut-off simulation of bilayers containing only uncharged molecules does not generate artefacts, nevertheless, the PME simulation gives generally better agreement with experimental data.

scholarly journals Conformation-dependent influences of hydrophobic amino acids in two in-register parallel β-sheet amyloids, an α-synuclein amyloid and a local structural model of PrPSc

2019 ◽  
Author(s):  
Hiroki Otaki ◽  
Yuzuru Taguchi ◽  
Noriyuki Nishida
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Prion Protein ◽  
Md Simulation ◽  
Structural Model ◽  
Prion Diseases ◽  
Md Simulations ◽  
Hydrophobic Residues ◽  
Prion Strains ◽  
Hydrophobic Amino Acids

AbstractPrions are pathogens that consist solely of abnormal isoforms of prion protein (PrPSc) without any genetic material. Therefore, they depend on purely protein-based mechanisms for diversification and maintenance of the pathogenetic information of prion strains. According to the protein-only hypothesis, the pathogenic properties of prions are determined by conformations of the constituent PrPSc, and alterations to even a single residue can drastically change the properties when the residue is located at a critical structural position of PrPSc. Interestingly, differences between polymorphic or species-specific residues responsible for the species/strain barriers are often caused by conservative replacements between hydrophobic amino acids. This implies that subtle differences among hydrophobic amino acids are significant for PrPSc structures. Specifically how the differences affect the structures is difficult to demonstrate due to the lack of detailed PrPSc structures. Here, we analyzed the influence of different hydrophobic residues on structures of an in-register parallel β-sheet amyloid of α-synuclein (αSyn) using molecular dynamics (MD) simulation, and applied the knowledge from the αSyn amyloid to design local structures of human PrPSc encompassing residues 107–143. The MD simulations of the αSyn amyloid revealed that methionine uniquely stabilized a U-shaped β-arch of the αSyn amyloid, whereas other hydrophobic amino acids destabilized the β-arch. Then, we assessed influence of the polymorphisms on the newly-designed model of PrPSc that are known to affect the clinical phenotypes of prion diseases. The MD simulations of the model also revealed unique effects of hydrophobic amino acids depending on regional structures. For example, G127V mutation that corresponds to a protective polymorphism against various human prion diseases greatly destabilized a U-shaped β-arch. Our study demonstrates specifically how and in what structures hydrophobic residues can exert unique effects on in-register parallel β-sheet amyloids and provides insights into the molecular mechanism of the strain diversity of prions and other pathogenic amyloids.Author SummaryPrions are unconventional pathogens that encode the pathogenic information in conformations of the constituent abnormal isoform of prion protein (PrPSc), independently of nucleotide genome. Therefore, conformational diversity of PrPSc underlies existence of many prion strains and species barriers of prions, although the conformations still remain undetermined. As prion/PrPSc propagates through refolding the host-encoded prion protein (PrPC) into the same conformation as itself, species barriers occur when the conformation of PrPSc is incompatible with the amino acid sequence of PrPC and the nascent PrPSc cannot stably maintain the structure. Interestingly, species barriers are often caused by a difference of a single hydrophobic residue. We investigated how the subtle differences between hydrophobic amino acids affect the structural stabilities of amyloids using molecular dynamics (MD) simulation of a newly designed local structural model of PrPSc, assuming that it has in-register parallel β-sheet structures. We have found that mutations equivalent to polymorphisms that cause barriers substantially affects the stabilities; for example, G127V mutation that makes the host resistant to various human prion diseases greatly destabilized the amyloid. The results support that PrPSc is an in-register parallel β-sheet amyloid and demonstrate the usefulness of MD simulation in investigation of species barriers of prions.

scholarly journals Inclusion complexes of β-cyclodextrin with tricyclic drugs: an X-ray diffraction, NMR and molecular dynamics study

2017 ◽  
Vol 13 ◽  
pp. 714-719 ◽  
Author(s):  
Franca Castiglione ◽  
Fabio Ganazzoli ◽  
Luciana Malpezzi ◽  
Andrea Mele ◽  
Walter Panzeri ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Solid State ◽  
Inclusion Complexes ◽  
Water Solution ◽  
Md Simulations ◽  
Conformational Transitions ◽  
X Ray Diffraction ◽  
X Ray ◽  
Fused Ring ◽  
Explicit Water

Tricyclic fused-ring cyclobenzaprine (1) and amitriptyline (2) form 1:1 inclusion complexes with β-cyclodextrin (β-CD) in the solid state and in water solution. Rotating frame NOE experiments (ROESY) showed the same geometry of inclusion for both 1/β-CD and 2/β-CD complexes, with the aromatic ring system entering the cavity from the large rim of the cyclodextrin and the alkylammonium chain protruding out of the cavity and facing the secondary OH rim. These features matched those found in the molecular dynamics (MD) simulations in solution and in the solid state from single-crystal X-ray diffraction of 1/β-CD and 2/β-CD complexes. The latter complex was found in a single conformation in the solid state, whilst the MD simulations in explicit water reproduced the conformational transitions observed experimentally for the free molecule.

scholarly journals Development of transferable coarse-grained models of amino acids

2020 ◽  
Vol 5 (3) ◽  
pp. 675-685 ◽  
Author(s):  
Olivia Conway ◽  
Yaxin An ◽  
Karteek K. Bejagam ◽  
Sanket A. Deshmukh
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Md Simulations ◽  
Peptide Amphiphiles ◽  
Coarse Grained ◽  
Explicit Solvent

We have developed transferable coarse-grained (CG) models of the twenty standard amino acids, which can be used to perform molecular dynamics (MD) simulations of peptide amphiphiles (PAs) in the presence of explicit solvent.

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