اشترك بالحزمة الذهبية واحصل على وصول غير محدود شمرا أكاديميا
تسجيل مستخدم جديدCooperatively enhanced reactivity and stabilitaxis of dissociating oligomeric proteins
84
0
0.0
(
0
)
اسأل ChatGPT حول البحث
ﻻ يوجد ملخص باللغة العربية
Many functional units in biology, such as enzymes or molecular motors, are composed of several subunits that can reversibly assemble and disassemble. This includes oligomeric proteins composed of several smaller monomers, as well as protein complexes assembled from a few proteins. By studying the generic spatial transport properties of such proteins, we investigate here whether their ability to reversibly associate and dissociate may confer them a functional advantage with respect to non-dissociating proteins. In uniform environments with position-independent association-dissociation, we find that enhanced diffusion in the monomeric state coupled to reassociation into the functional oligomeric form leads to enhanced reactivity with distant targets. In non-uniform environments with position-dependent association-dissociation, caused e.g. by spatial gradients of an inhibiting chemical, we find that dissociating proteins generically tend to accumulate in regions where they are most stable, a process that we term stabilitaxis.
قيم البحث
اقرأ أيضاً
Many enhanced sampling methods, such as Umbrella Sampling, Metadynamics or Variationally Enhanced Sampling, rely on the identification of appropriate collective variables. For proteins, even small ones, finding appropriate collective variables has pr
oven challenging. Here we suggest that the NMR $S^2$ order parameter can be used to this effect. We trace the validity of this statement to the suggested relation between $S^2$ and entropy. Using the $S^2$ order parameter and a surrogate for the protein enthalpy in conjunction with Metadynamics or Variationally Enhanced Sampling we are able to reversibly fold and unfold a small protein and draw its free energy at a fraction of the time that is needed in unbiased simulations. From a more conceptual point of view this implies describing folding as a resulting from a trade off between entropy and enthalpy. We also use $S^2$ in combination with the free energy flooding method to compute the unfolding rate of this peptide. We repeat this calculation at different temperatures to obtain the unfolding activation energy.
Nuclear quantum effects, such as zero-point energy and tunneling, cause significant changes to the structure and dynamics of hydrogen bonded systems such as liquid water. However, due to the current inability to simulate liquid water using an exact d
escription of its electronic structure, the interplay between nuclear and electronic quantum effects remains unclear. Here we use simulations that incorporate the quantum mechanical nature of both the nuclei and electrons to provide a fully ab initio determination of the particle quantum kinetic energies, free energy change upon exchanging hydrogen for deuterium and the isotope fractionation ratio in water. These properties, which selectively probe the quantum nature of the nuclear degrees of freedom, allow us to make direct comparison to recent experiments and elucidate how electronic exchange and correlation and nuclear quantum fluctuations determine the structure of the hydrogen bond in water.
Although ligand-binding sites in many proteins contain a high number density of charged side chains that can polarize small organic molecules and influence binding, the magnitude of this effect has not been studied in many systems. Here, we use a qua
ntum mechanics/molecular mechanics (QM/MM) approach in which the ligand is the QM region to compute the ligand polarization energy of 286 protein-ligand complexes from the PDBBind Core Set (release 2016). We observe that the ligand polarization energy is linearly correlated with the magnitude of the electric field acting on the ligand, the magnitude of the induced dipole moment, and the classical polarization energy. The influence of protein and cation charges on the ligand polarization diminishes with the distance and is below 2 kcal/mol at 9 $unicode{x212B}$ and 1 kcal/mol at 12 $unicode{x212B}$. Considering both polarization and solvation appears essential to computing negative binding energies in some crystallographic complexes. Solvation, but not polarization, is essential for achieving moderate correlation with experimental binding free energies.
Adding salt to water at ambient pressure affects its thermodynamic properties. At low salt concentration, anomalies such as the density maximum are shifted to lower temperature, while at large enough salt concentration they cannot be observed any mor
e. Here we investigate the effect of salt on an anomaly recently observed in pure water at negative pressure: the existence of a sound velocity minimum along isochores. We compare experiments and simulations for an aqueous solution of sodium chloride with molality around $1.2,mathrm{mol,kg^{-1}}$, reaching pressures beyond $-100,mathrm{MPa}$. We also discuss the origin of the minima in the sound velocity and emphasize the importance of the relative position of the temperatures of sound velocity and density anomalies.
We propose an improved prediction method of the tertiary structures of $alpha$-helical membrane proteins based on the replica-exchange method by taking into account helix deformations. Our method allows wide applications because transmembrane helices
of native membrane proteins are often distorted. In order to test the effectiveness of the present method, we applied it to the structure predictions of glycophorin A and phospholamban. The results were in accord with experiments.
سجل دخول لتتمكن من نشر تعليقات
التعليقات
جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
