اشترك بالحزمة الذهبية واحصل على وصول غير محدود شمرا أكاديميا
تسجيل مستخدم جديدCollective Molecular Dynamics in Proteins and Membranes
226
0
0.0
(
0
)
تأليف
Maikel C. Rheinstadter
اسأل ChatGPT حول البحث
ﻻ يوجد ملخص باللغة العربية
The understanding of dynamics and functioning of biological membranes and in particular of membrane embedded proteins is one of the most fundamental problems and challenges in modern biology and biophysics. In particular the impact of membrane composition and properties and of structure and dynamics of the surrounding hydration water on protein function is an upcoming hot topic, which can be addressed by modern experimental and computational techniques. Correlated molecular motions might play a crucial role for the understanding of, for instance, transport processes and elastic properties, and might be relevant for protein function. Experimentally that involves determining dispersion relations for the different molecular components, i.e., the length scale dependent excitation frequencies and relaxation rates. Only very few experimental techniques can access dynamical properties in biological materials on the nanometer scale, and resolve dynamics of lipid molecules, hydration water molecules and proteins and the interaction between them. In this context, inelastic neutron scattering turned out to be a very powerful tool to study dynamics and interactions in biomolecular materials up to relevant nanosecond time scales and down to the nanometer length scale. We review and discuss inelastic neutron scattering experiments to study membrane elasticity and protein-protein interactions of membrane embedded proteins.
قيم البحث
اقرأ أيضاً
We use coarse grained molecular dynamics simulations to investigate diffusion properties of sheared lipid membranes with embedded transmembrane proteins. In membranes without proteins, we find normal in-plane diffusion of lipids in all flow condition
s. Protein embedded membranes behave quite differently: by imposing a simple shear flow and sliding the monolayers of the membrane over each other, the motion of protein clusters becomes strongly superdiffusive in the shear direction. In such a circumstance, subdiffusion regime is predominant perpendicular to the flow. We show that superdiffusion is a result of accelerated chaotic motions of protein--lipid complexes within the membrane voids, which are generated by hydrophobic mismatch or the transport of lipids by proteins.
Cytoskeletal motor proteins are involved in major intracellular transport processes which are vital for maintaining appropriate cellular function. The motor exhibits distinct states of motility: active motion along filaments, and effectively stationa
ry phase in which it detaches from the filaments and performs passive diffusion in the vicinity of the detachment point due to cytoplasmic crowding. The transition rates between motion and pause phases are asymmetric in general, and considerably affected by changes in environmental conditions which influences the efficiency of cargo delivery to specific targets. By considering the motion of molecular motor on a single filament as well as a dynamic filamentous network, we present an analytical model for the dynamics of self-propelled particles which undergo frequent pause phases. The interplay between motor processivity, structural properties of filamentous network, and transition rates between the two states of motility drastically changes the dynamics: multiple transitions between different types of anomalous diffusive dynamics occur and the crossover time to the asymptotic diffusive or ballistic motion varies by several orders of magnitude. We map out the phase diagrams in the space of transition rates, and address the role of initial conditions of motion on the resulting dynamics.
Assessing the structural properties of large proteins is important to gain an understanding of their function in, e.g., biological systems or biomedical applications. We propose a method to examine the mechanical properties of proteins subject to app
lied forces by means of multiscale simulation. We consider both stretching and torsional forces, which can be applied independently of each other. We apply torsional forces to a coarse-grained continuum model of the antibody protein immunoglobulin G (IgG) using Fluctuating Finite Element Analysis and identify the area of strongest deformation. This region is essential to the torsional properties of the molecule as a whole, as it represents the softest, most deformable domain. We subject this part of the molecule to torques and stretching forces on an atomistic level, using molecular dynamics simulations, in order to investigate its torsional properties. We calculate the torsional resistance as a function of the rotation of the domain, while subjecting it to various stretching forces. We learn how these obtained torsion profiles evolve with increasing stretching force and show that they exhibit torsion stiffening, which is in qualitative agreement with experimental findings. We argue that combining the torsion profiles for various stretching forces effectively results in a combined force-torque spectroscopy analysis, which may serve as a mechanical signature for the examined molecule.
A number of recently discovered protein structures incorporate a rather unexpected structural feature: a knot in the polypeptide backbone. These knots are extremely rare, but their occurrence is likely connected to protein function in as yet unexplor
ed fashion. Our analysis of the complete Protein Data Bank reveals several new knots which, along with previously discovered ones, can shed light on such connections. In particular, we identify the most complex knot discovered to date in human ubiquitin hydrolase, and suggest that its entangled topology protects it against unfolding and degradation by the proteasome. Knots in proteins are typically preserved across species and sometimes even across kingdoms. However, we also identify a knot which only appears in some transcarbamylases while being absent in homologous proteins of similar structure. The emergence of the knot is accompanied by a shift in the enzymatic function of the protein. We suggest that the simple insertion of a short DNA fragment into the gene may suffice to turn an unknotted into a knotted structure in this protein.
Cells coexist together in colonies or as tissues. Their behaviour is controlled by an interplay between intercellular forces and biochemical regulation. We develop a simple model of the cell cycle, the fundamental regulatory network controlling growt
h and division, and couple this to the physical forces arising within the cell collective. We analyse this model using both particle-based computer simulations and a continuum theory. We focus on 2D colonies confined in a channel. These develop moving growth fronts of dividing cells with quiescent cells in the interior. The profile and speed of these fronts are non-trivially related to the substrate friction and the cell cycle parameters, providing a possible approach to measure such parameters in experiments.
سجل دخول لتتمكن من نشر تعليقات
التعليقات
جاري جلب التعليقات
سجل دخول لتتمكن من متابعة معايير البحث التي قمت باختيارها
