ترغب بنشر مسار تعليمي؟ اضغط هنا

On the Classical Vibrational Coherence of Carbonyl Groups in the Selectivity Filter Backbone of KcsA Ion Channel

276   0   0.0 ( 0 )
 نشر من قبل Vahid Salari
 تاريخ النشر 2015
  مجال البحث علم الأحياء فيزياء
والبحث باللغة English




اسأل ChatGPT حول البحث

It has been suggested that quantum coherence in the selectivity filter of ion channel may play a key role in fast conduction and selectivity of ions. However, it has not been clearly elucidated yet why classical coherence is not sufficient for this purpose. In this paper, we investigate the classical vibrational coherence between carbonyl groups oscillations in the selectivity filter of KcsA ion channels based on the data obtained from molecular dynamics simulations. Our results show that classical coherence plays no effective role in fast ionic conduction.

قيم البحث

اقرأ أيضاً

We introduce a self-consistent multi-species kinetic theory based on the structure of the narrow voltage-gated potassium channel. Transition rates depend on a complete energy spectrum with contributions including the dehydration amongst species, inte raction with the dipolar charge of the filter and, bulk solution properties. It displays high selectivity between species coexisting with fast conductivity, and Coulomb blockade phenomena, and it fits well to data.
Understanding the mechanisms underlying ion channel function from the atomic-scale requires accurate ab initio modelling as well as careful experiments. Here, we present a density functional theory (DFT) study of the ion channel gramicidin A, whose i nner pore conducts only monovalent cations and whose conductance has been shown to depend on the side chains of the amino acids in the channel. We investigate the ground-state geometry and electronic properties of the channel in vacuum, focusing on their dependence on the side chains of the amino acids. We find that the side chains affect the ground state geometry, while the electrostatic potential of the pore is independent of the side chains. This study is also in preparation for a full, linear scaling DFT study of gramicidin A in a lipid bilayer with surrounding water. We demonstrate that linear scaling DFT methods can accurately model the system with reasonable computational cost. Linear scaling DFT allows ab initio calculations with 10,000 to 100,000 atoms and beyond, and will be an important new tool for biomolecular simulations.
The nicotinic acetylcholine receptor (nAChR) is the prototypic member of the `Cys-loop superfamily of ligand-gated ion channels which mediate synaptic neurotransmission, and whose other members include receptors for glycine, gamma-aminobutyric acid, and serotonin. Cryo-electron microscopy has yielded a three dimensional structure of the nAChR in its closed state. However, the exact nature and location of the channel gate remains uncertain. Although the transmembrane pore is constricted close to its center, it is not completely occluded. Rather, the pore has a central hydrophobic zone of radius about 3 A. Model calculations suggest that such a constriction may form a hydrophobic gate, preventing movement of ions through a channel. We present a detailed and quantitative simulation study of the hydrophobic gating model of the nicotinic receptor, in order to fully evaluate this hypothesis. We demonstrate that the hydrophobic constriction of the nAChR pore indeed forms a closed gate. Potential of mean force (PMF) calculations reveal that the constriction presents a barrier of height ca. 10 kT to the permeation of sodium ions, placing an upper bound on the closed channel conductance of 0.3 pS. Thus, a 3 A radius hydrophobic pore can form a functional barrier to the permeation of a 1 A radius Na+ ion. Using a united atom force field for the protein instead of an all atom one retains the qualitative features but results in differing conductances, showing that the PMF is sensitive to the detailed molecular interactions.
We analytically derive the lower bound of the total conformational energy of a protein structure by assuming that the total conformational energy is well approximated by the sum of sequence-dependent pairwise contact energies. The condition for the n ative structure achieving the lower bound leads to the contact energy matrix that is a scalar multiple of the native contact matrix, i.e., the so-called Go potential. We also derive spectral relations between contact matrix and energy matrix, and approximations related to one-dimensional protein structures. Implications for protein structure prediction are discussed.
Small-angle X-ray scattering (SAXS) experiments are increasingly used to probe RNA structure. A number of emph{forward models} that relate measured SAXS intensities and structural features, and that are suitable to model either explicit-solvent effec ts or solute dynamics, have been proposed in the past years. Here we introduce an approach that integrates atomistic molecular dynamics simulations and SAXS experiments to reconstruct RNA structural ensembles while simultaneously accounting for both RNA conformational dynamics and explicit-solvent effects. Our protocol exploits SAXS pure-solute forward models and enhanced sampling methods to sample an heterogenous ensemble of structures, with no information towards the experiments provided on-the-fly. The generated structural ensemble is then reweighted through the maximum entropy principle so as to match reference SAXS experimental data at multiple ionic conditions. Importantly, accurate explicit-solvent forward models are used at this reweighting stage. We apply this framework to the GTPase-associated center, a relevant RNA molecule involved in protein translation, in order to elucidate its ion-dependent conformational ensembles. We show that (a) both solvent and dynamics are crucial to reproduce experimental SAXS data and (b) the resulting dynamical ensembles contain an ion-dependent fraction of extended structures.
التعليقات
جاري جلب التعليقات جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
mircosoft-partner

هل ترغب بارسال اشعارات عن اخر التحديثات في شمرا-اكاديميا