scholarly journals Ligand-induced structural changes analysis of ribose-binding protein as studied by molecular dynamics simulations

2021 ◽  
pp. 1-12
Author(s):  
Haiyan Li ◽  
Zanxia Cao ◽  
Guodong Hu ◽  
Liling Zhao ◽  
Chunling Wang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Structural Changes ◽  
Binding Protein ◽  
Network Models ◽  
Md Simulations ◽  
Protein Domain ◽  
Opening Angle ◽  
Conformation Changes ◽  
Wide Range ◽  
Ribose Binding Protein

BACKGROUND: The ribose-binding protein (RBP) from Escherichia coli is one of the representative structures of periplasmic binding proteins. Binding of ribose at the cleft between two domains causes a conformational change corresponding to a closure of two domains around the ligand. The RBP has been crystallized in the open and closed conformations. OBJECTIVE: With the complex trajectory as a control, our goal was to study the conformation changes induced by the detachment of the ligand, and the results have been revealed from two computational tools, MD simulations and elastic network models. METHODS: Molecular dynamics (MD) simulations were performed to study the conformation changes of RBP starting from the open-apo, closed-holo and closed-apo conformations. RESULTS: The evolution of the domain opening angle θ clearly indicates large structural changes. The simulations indicate that the closed states in the absence of ribose are inclined to transition to the open states and that ribose-free RBP exists in a wide range of conformations. The first three dominant principal motions derived from the closed-apo trajectories, consisting of rotating, bending and twisting motions, account for the major rearrangement of the domains from the closed to the open conformation. CONCLUSIONS: The motions showed a strong one-to-one correspondence with the slowest modes from our previous study of RBP with the anisotropic network model (ANM). The results obtained for RBP contribute to the generalization of robustness for protein domain motion studies using either the ANM or PCA for trajectories obtained from MD.

scholarly journals A hierarchical Bayesian framework for force field selection in molecular dynamics simulations

2016 ◽  
Vol 374 (2060) ◽  
pp. 20150032 ◽  
Author(s):  
S. Wu ◽  
P. Angelikopoulos ◽  
C. Papadimitriou ◽  
R. Moser ◽  
P. Koumoutsakos
Keyword(s):  
Experimental Data ◽  
Molecular Dynamics ◽  
Force Field ◽  
Computational Cost ◽  
Md Simulations ◽  
Bayesian Framework ◽  
Underlying Structure ◽  
Hierarchical Bayesian ◽  
Wide Range ◽  
Selection Of

We present a hierarchical Bayesian framework for the selection of force fields in molecular dynamics (MD) simulations. The framework associates the variability of the optimal parameters of the MD potentials under different environmental conditions with the corresponding variability in experimental data. The high computational cost associated with the hierarchical Bayesian framework is reduced by orders of magnitude through a parallelized Transitional Markov Chain Monte Carlo method combined with the Laplace Asymptotic Approximation. The suitability of the hierarchical approach is demonstrated by performing MD simulations with prescribed parameters to obtain data for transport coefficients under different conditions, which are then used to infer and evaluate the parameters of the MD model. We demonstrate the selection of MD models based on experimental data and verify that the hierarchical model can accurately quantify the uncertainty across experiments; improve the posterior probability density function estimation of the parameters, thus, improve predictions on future experiments; identify the most plausible force field to describe the underlying structure of a given dataset. The framework and associated software are applicable to a wide range of nanoscale simulations associated with experimental data with a hierarchical structure.

scholarly journals Mechanistic picture for chemo-mechanical couplings in a bacterial proton-coupled oligopeptide transporter from Streptococcus thermophilus

2020 ◽  
Author(s):  
Kalyan Immadisetty ◽  
Mahmoud Moradi
Keyword(s):  
Molecular Dynamics ◽  
Cell Membrane ◽  
Proton Transport ◽  
Structural Changes ◽  
Streptococcus Thermophilus ◽  
Md Simulations ◽  
Electrochemical Gradient ◽  
Binding Region ◽  
Conformational Switch ◽  
Sequence Identity

AbstractProton-coupled oligopeptide transporters (POTs) use the proton electrochemical gradient to transport peptides across the cell membrane. Despite the significant biological and biomedical relevance of these proteins, a detailed mechanistic picture for chemo-mechanical couplings involved in substrate/proton transport and protein structural changes is missing. We therefore performed microsecond-level molecular dynamics (MD) simulations of bacterial POT transporter PepTSt, which shares ~80% sequence identity with the human POT, PepT1, in the substrate binding region. Three different conformational states of PepTSt were simulated including, (i) occluded, apo, (ii) inward-facing, apo, and (iii) inward-facingoccluded, Leu-Ala bound. We propose that the interaction of R33 with E299 and E300 acts as a conformational switch (i.e., to trigger the conformational change from an inward-to outward-facing state) in the substrate transport. Additionally, E299 and E400 should disengage from interacting with the substrate either through protonation or through co-ordination with a cation for the substrate to get transported.

Structural changes in retinol binding protein induced by retinol removal. A molecular dynamics study

1986 ◽  
Vol 139 (2) ◽  
pp. 564-570 ◽  
Author(s):  
P. Sandblom ◽  
J. Åqvist ◽  
T.A. Jones ◽  
M.E. Newcomer ◽  
W.F. van Gunsteren ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Structural Changes ◽  
Binding Protein ◽  
Retinol Binding Protein

Hydration Structure and Shear Viscosity of Water Nanoconfined Between Mica Surfaces

2006 ◽  
Author(s):  
Yongsheng Leng ◽  
Peter T. Cummings
Keyword(s):  
Molecular Dynamics ◽  
Liquid Phase ◽  
Shear Rate ◽  
Shear Viscosity ◽  
Surface Force ◽  
Md Simulations ◽  
Force Balance ◽  
Density Distributions ◽  
Wide Range ◽  
Hydration Layers

Molecular dynamics (MD) simulations have been performed to investigate the structure, shear viscosity and dynamics of hydration layers of the thickness of D = 0.61 ∼ 2.44 nm confined between two mica surfaces. For D = 0.92 ∼ 2.44 nm films, water O density distributions indicate that the hydration layers are in liquid phase. The corresponding shear responses are fluidic and similar to those observed in surface force balance (SFB) experiment. However, further increase in confinement leads to the formation of a bilayer ice (D = 0.61 nm) which shows significant shear enhancement and shear thinning over a wide range of shear rate in MD regime, consistent with recent experimental results by shear resonant apparatus for the two mica surfaces in registry.

scholarly journals Thermodynamics, dynamics, and structure of supercritical water at extreme conditions

2020 ◽  
Vol 22 (28) ◽  
pp. 16051-16062 ◽  
Author(s):  
Tae Jun Yoon ◽  
Lara A. Patel ◽  
Taeho Ju ◽  
Matthew J. Vigil ◽  
Alp T. Findikoglu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Supercritical Water ◽  
Structural Changes ◽  
Md Simulations ◽  
Extreme Conditions ◽  
Melting Line

Molecular dynamics (MD) simulations to understand the thermodynamic, dynamic, and structural changes in supercritical water across the Frenkel line and the melting line have been performed.

A Molecular Dynamics Simulation Study Towards Understanding the Effects of Diameter and Chirality on Hydrogen Adsorption in Singlewalled Carbon Nanotubes

2003 ◽  
Vol 801 ◽  
Author(s):  
Hansong Cheng ◽  
Alan C. Cooper ◽  
Guido P. Pez ◽  
Milen K. Kostov ◽  
Milton W. Cole ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Molecular Dynamics ◽  
Hydrogen Adsorption ◽  
Md Simulations ◽  
Substantial Effect ◽  
Dynamics Simulation ◽  
Physical Parameters ◽  
Wide Range ◽  
Field Methodology ◽  
Molecular Forces

ABSTRACTA force field methodology has been developed for the description of carbon-carbon and carbon-molecular hydrogen interactions that is ideally suited to modeling hydrogen adsorption on single-walled carbon nanotubes (SWNT). The method makes use of existing parameters of potential functions developed for sp2 and sp3 hybridized carbon atoms and allows accurate representation of molecular forces on curved carbon surfaces. This approach has been used in molecular dynamics (MD) simulations for hydrogen adsorption in SWNT. The results reveal significant nanotube deformations, consistent with ab initio MD simulations, and the calculated energies of adsorption at room temperature are comparable to the reported experimental heats of adsorption for H2 in SWNT. The efficiency of this new method has permitted the MD simulation of hydrogen adsorption on a wide range of SWNT types, varying such parameters as nanotube diameter and chirality. The results show that these SWNT physical parameters have a substantial effect on the energies of adsorption and hydrogen capacities.

scholarly journals 3D-QSAR, Molecular Docking, and MD Simulations of Anthraquinone Derivatives as PGAM1 Inhibitors

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuwei Wang ◽  
Yifan Guo ◽  
Shaojia Qiang ◽  
Ruyi Jin ◽  
Zhi Li ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Rational Design ◽  
Binding Free Energy ◽  
3D Qsar ◽  
Md Simulations ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Wide Range ◽  
Anthraquinone Derivatives

PGAM1 is overexpressed in a wide range of cancers, thereby promoting cancer cell proliferation and tumor growth, so it is gradually becoming an attractive target. Recently, a series of inhibitors with various structures targeting PGAM1 have been reported, particularly anthraquinone derivatives. In present study, the structure–activity relationships and binding mode of a series of anthraquinone derivatives were probed using three-dimensional quantitative structure–activity relationships (3D-QSAR), molecular docking, and molecular dynamics (MD) simulations. Comparative molecular field analysis (CoMFA, r2 = 0.97, q2 = 0.81) and comparative molecular similarity indices analysis (CoMSIA, r2 = 0.96, q2 = 0.82) techniques were performed to produce 3D-QSAR models, which demonstrated satisfactory results, especially for the good predictive abilities. In addition, molecular dynamics (MD) simulations technology was employed to understand the key residues and the dominated interaction between PGAM1 and inhibitors. The decomposition of binding free energy indicated that the residues of F22, K100, V112, W115, and R116 play a vital role during the ligand binding process. The hydrogen bond analysis showed that R90, W115, and R116 form stable hydrogen bonds with PGAM1 inhibitors. Based on the above results, 7 anthraquinone compounds were designed and exhibited the expected predictive activity. The study explored the structure–activity relationships of anthraquinone compounds through 3D-QSAR and molecular dynamics simulations and provided theoretical guidance for the rational design of new anthraquinone derivatives as PGAM1 inhibitors.

Sign in / Sign up

Export Citation Format

Share Document