اشترك بالحزمة الذهبية واحصل على وصول غير محدود شمرا أكاديميا
تسجيل مستخدم جديدQuantum Theory on Glucose Transport Across Membrane
384
0
0.0
(
0
)
تأليف
Liaofu Luo
اسأل ChatGPT حول البحث
ﻻ يوجد ملخص باللغة العربية
After a brief review of the protein folding quantum theory and a short discussion on its experimental evidences the mechanism of glucose transport across membrane is studied from the point of quantum conformational transition. The structural variations among four kinds of conformations of the human glucose transporter GLUT1 (ligand free occluded, outward open, ligand bound occluded and inward open) are looked as the quantum transition. The comparative studies between mechanisms of uniporter (GLUT1) and symporter (XylE and GlcP) are given. The transitional rates are calculated from the fundamental theory. The monosaccharide transport kinetics is proposed. The steady state of the transporter is found and its stability is studied. The glucose (xylose) translocation rates in two directions and in different steps are compared. The mean transport time in a cycle is calculated and based on it the comparison of the transport times between GLUT1,GlcP and XylE can be drawn. The non-Arrhenius temperature dependence of the transition rate and the mean transport time is predicted. It is suggested that the direct measurement of temperature dependence is a useful tool for deeply understanding the transmembrane transport mechanism.
قيم البحث
اقرأ أيضاً
The molecular mechanism of ion channel gating and substrate modulation is elusive for many voltage gated ion channels, such as eukaryotic sodium ones. The understanding of channel functions is a pressing issue in molecular biophysics and biology. Mat
hematical modeling, computation and analysis of membrane channel charge transport have become an emergent field and give rise to significant contributions to our understanding of ion channel gating and function. This review summarizes recent progresses and outlines remaining challenges in mathematical modeling, simulation and analysis of ion channel charge transport. One of our focuses is the Poisson-Nernst-Planck (PNP) model and its generalizations. Specifically, the basic framework of the PNP system and some of its extensions, including size effects, ion-water interactions, coupling with density functional theory and relation to fluid flow models. A reduced theory, the Poisson- Boltzmann-Nernst-Planck (PBNP) model, and a differential geometry based ion transport model are also discussed. For proton channel, a multiscale and multiphysics Poisson-Boltzmann-Kohn-Sham (PBKS) model is presented. We show that all of these ion channel models can be cast into a unified variational multiscale framework with a macroscopic continuum domain of the solvent and a microscopic discrete domain of the solute. The main strategy is to construct a total energy functional of a charge transport system to encompass the polar and nonpolar free energies of solvation and chemical potential related energies. Current computational algorithms and tools for numerical simulations and results from mathematical analysis of ion channel systems are also surveyed.
Computational prediction of membrane protein (MP) structures is very challenging partially due to lack of sufficient solved structures for homology modeling. Recently direct evolutionary coupling analysis (DCA) sheds some light on protein contact pre
diction and accordingly, contact-assisted folding, but DCA is effective only on some very large-sized families since it uses information only in a single protein family. This paper presents a deep transfer learning method that can significantly improve MP contact prediction by learning contact patterns and complex sequence-contact relationship from thousands of non-membrane proteins (non-MPs). Tested on 510 non-redundant MPs, our deep model (learned from only non-MPs) has top L/10 long-range contact prediction accuracy 0.69, better than our deep model trained by only MPs (0.63) and much better than a representative DCA method CCMpred (0.47) and the CASP11 winner MetaPSICOV (0.55). The accuracy of our deep model can be further improved to 0.72 when trained by a mix of non-MPs and MPs. When only contacts in transmembrane regions are evaluated, our method has top L/10 long-range accuracy 0.62, 0.57, and 0.53 when trained by a mix of non-MPs and MPs, by non-MPs only, and by MPs only, respectively, still much better than MetaPSICOV (0.45) and CCMpred (0.40). All these results suggest that sequence-structure relationship learned by our deep model from non-MPs generalizes well to MP contact prediction. Improved contact prediction also leads to better contact-assisted folding. Using only top predicted contacts as restraints, our deep learning method can fold 160 and 200 of 510 MPs with TMscore>0.6 when trained by non-MPs only and by a mix of non-MPs and MPs, respectively, while CCMpred and MetaPSICOV can do so for only 56 and 77 MPs, respectively. Our contact-assisted folding also greatly outperforms homology modeling.
Understanding protein folding has been one of the great challenges in biochemistry and molecular biophysics. Over the past 50 years, many thermodynamic and kinetic studies have been performed addressing the stability of globular proteins. In comparis
on, advances in the membrane protein folding field lag far behind. Although membrane proteins constitute about a third of the proteins encoded in known genomes, stability studies on membrane proteins have been impaired due to experimental limitations. Furthermore, no systematic experimental strategies are available for folding these biomolecules in vitro. Common denaturing agents such as chaotropes usually do not work on helical membrane proteins, and ionic detergents have been successful denaturants only in few cases. Refolding a membrane protein seems to be a craftsman work, which is relatively straightforward for transmembrane {beta}-barrel proteins but challenging for {alpha}-helical membrane proteins. Additional complexities emerge in multidomain membrane proteins, data interpretation being one of the most critical. In this review, we will describe some recent efforts in understanding the folding mechanism of membrane proteins that have been reversibly refolded allowing both thermodynamic and kinetic analysis. This information will be discussed in the context of current paradigms in the protein folding field.
Computational elucidation of membrane protein (MP) structures is challenging partially due to lack of sufficient solved structures for homology modeling. Here we describe a high-throughput deep transfer learning method that first predicts MP contacts
by learning from non-membrane proteins (non-MPs) and then predicting three-dimensional structure models using the predicted contacts as distance restraints. Tested on 510 non-redundant MPs, our method has contact prediction accuracy at least 0.18 better than existing methods, predicts correct folds for 218 MPs (TMscore at least 0.6), and generates three-dimensional models with RMSD less than 4 Angstrom and 5 Angstrom for 57 and 108 MPs, respectively. A rigorous blind test in the continuous automated model evaluation (CAMEO) project shows that our method predicted high-resolution three-dimensional models for two recent test MPs of 210 residues with RMSD close to 2 Angstrom. We estimated that our method could predict correct folds for between 1,345 and 1,871 reviewed human multi-pass MPs including a few hundred new folds, which shall facilitate the discovery of drugs targeting at membrane proteins.
Membrane transporters contribute to the regulation of the internal environment of cells by translocating substrates across cell membranes. Like all physical systems, the behaviour of membrane transporters is constrained by the laws of thermodynamics.
However, many mathematical models of transporters, especially those incorporated into whole-cell models, are not thermodynamically consistent, leading to unrealistic behaviour. In this paper we use a physics-based modelling framework, in which the transfer of energy is explicitly accounted for, to develop thermodynamically consistent models of transporters. We then apply this methodology to model two specific transporters: the cardiac sarcoplasmic/endoplasmic Ca$^{2+}$ ATPase (SERCA) and the cardiac Na$^+$/K$^+$ ATPase.
سجل دخول لتتمكن من نشر تعليقات
التعليقات
جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
