1,721,193 research outputs found
Nitrogen fixation by a biologically-inspired catalyst: An ab initio and hybrid qm/mm molecular dynamics study
No full textMolecular Modeling of Ion Channels: Structural Predictions
No full textRecent advances in membrane protein crystallography have greatly increased structural information of channels permeating metal ions. Structural bioinformatics techniques and molecular dynamics calculations are providing structural models of ion channels for which the three-dimensional structure is not known. Most of the reported structure prediction studies focus on K(+) channels and are based on the KcsA K(+) channel structure
Ab initio molecular dynamics simulations of biologically relevant systems
No full textAb initio (Car-Parrinello) molecular dynamics (AIMD) simulations [1] are increasingly used to investigate structural, dynamical, energetic and electronic properties of biomolecules. At opposite to classical MD simulations, in this approach the underlying potential energy surface is calculated directly from first-principles. This leads to a parameter free molecular dynamics, where interatomic forces are not empirically derived, but are evaluated from electronic structure calculations as the simulations proceeds
Potassium permeation through the KcsA channel: a density functional study
No full textWe present a theoretical study on structural and electronic aspects of K+ permeation through the binding sites of the KcsA channel's selectivity filter. Density functional calculations are carried out on models taken from selected snapshots of a molecular dynamics simulation recently reported [FEBS Lett. 477 (2000) 37]. During the translocation process from one binding site to the other, the coordination number of the permeating K+ ion turns out to decrease and K+ ion polarizes significantly its ligands, backbone carbonyl groups and a water molecule. K+-induced polarization increases significantly at the transition state ITS) between the two binding sites. These findings suggest that polarization effects play a significant role in the microscopic mechanisms regulating potassium permeation. (C) 2002 Elsevier Science B.V All rights reserved
Nitrogen fixation by a molybdenum catalyst mimicking the function of the nitrogenase enzyme: A critical evaluation of DFT and solvent effects
No full textCompounds mimicking the enzyme nitrogenase represent promising alternative routes to the current Haber-Bosch industrial synthesis of ammonia from molecular hydrogen and nitrogen. In this work, we investigated the full catalytic cycle of one of such compounds, Mo(HIPTN3N) (with HIPT = hexaisopropylterphenyl), by means of DFT calculations. Our results suggest these large ligands to exert mainly a steric influence on the structural properties of the catalyst. In addition, we provided a structural and electronic characterization of the putative reaction intermediates along with a picture of the electronic mechanism of molecular nitrogen N-N bond breaking. A large discrepancy was observed between calculated and experimental reaction free energies, suggesting that in the present case the predictability of DFT reaction energies is limited. Investigation of explicit solvation of specific catalytic intermediates as well as of the protonation and reducing agents reveal the crucial role played by the solvent molecules (benzene and heptane) particularly for protonation steps. Furthermore, the analysis of several DFT functionals indicates that these have to be carefully chosen in order to reproduce the energetic profile of reduction steps. This study shows how DFT calculations may be a powerful tool to describe structural and electronic properties of the intermediates of the catalytic cycle, yet, due to the complexity of the system, reaction energies cannot be easily reproduced without a careful choice of the solvation model and the exchange-correlation functional
Potassium and sodium binding to the outer mouth of the K+ channel l
No full textMolecular dynamics simulations of the K+ channel from Streptomyces lividans (KcsA channel) were performed in a membrane-mimetic environment with Na+ and K+ in different initial locations. The structure of the channel remained stable and well preserved for simulations lasting up to 1.5 ns. Salt bridges between Asp80 and Arg89 of neighboring subunits, not detected in the X-ray structure, enhanced the stability of the tetrameric structure. Na+ or K+ ions located in the channel vestibule lost part of their hydration shell and diffused into the channel inner pore in less than a few hundred picoseconds. This powerful catalytic action was caused by strong electrostatic interactions with Asp80 and Glu71. The hydration state of the metal ions turned out to depend significantly on the conformational flexibility of the channel. Furthermore, Na+ entered the channel inner pore bound to more water molecules than K+. The different hydration state of the two ions may be a determinant factor in the ion selectivity of the channel
Drug permeation through the cell membrane and OmpF investigated by Molecular Dynamics Simulations
No full textMolecular dynamics simulations of the NGF-TrkA domain 5 complex and comparison with biological data
No full textThe nerve growth factor (NGF) is an important pharmacological target for Alzheimer's and other neurodegenerative diseases. Its action derives partly from its binding to the tyrosine kinase A receptor (TrkA). Here we study energetics and dynamics of the NGF-TrkA complex by carrying out multinanosecond molecular dynamics simulations, accompanied by electrostatic calculations based on the Poisson-Boltzmann equation. Our calculations, which are based on the x-ray structure of the complex, suggest that some of the mutations affecting dramatically the affinity of the complex involve residues that form highly favorable, direct or water-mediated hydrogen bond interactions at the ligand-receptor interface and, in some cases, that also critically participate to the large-scale motions of the complex. Furthermore, our calculations offer a rationale for the small effect on binding affinity observed upon specific mutations involving large changes in electrostatics (i.e., the charged-to-neutral mutations). Finally, these calculations, used along with the mutagenesis data, provide a basis for designing new peptides that mimic NGF in TrkA binding function
- …
