相关论文: Simulations of Oligomeric Intermediates in Prion D…
Prions are proteinaceous infectious particles that cause neurodegenerative diseases in humans and animals. The complex nature of prions, with respect to their conformations and aggregations, has been an important area of research for quite…
Motivated by the biologically important and complex phenomena of A\beta\ peptide aggregation in Alzheimer's disease, we introduce a model and simulation methodology for studying protein aggregation that includes extra-cellular aggregation,…
Neurodegenerative diseases are associated with the assembly of specific proteins into oligomers and fibrillar aggregates. At the brain scale, these protein assemblies can diffuse through the brain and seed other regions, creating an…
We simulate a two-dimensional, lattice based, protein-level statistical mechanical model for prion diseases (e.g., Mad Cow disease) with concommitant prion protein misfolding and aggregation. Our simulations lead us to the hypothesis that…
The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention since it has been associated with neurodegenerative conditions such as Alzheimer's and Parkinson's…
We present a theory for the laboratory and epidemiological data for incubation times in infectious prion diseases. The central feature of our model is that slow growth of misfolded protein-aggregates from small initial seeds controls the…
The need to understand the assembly kinetics of fibril formation has become urgent because of the realization that soluble oligomers of amyloidogenic peptides may be even more neurotoxic than the end product, namely, the amyloid fibrils. In…
We consider a model for the polymerization (fragmentation) process involved in infectious prion self-replication and study both its dynamics and non-zero steady state. We address several issues. Firstly, we give conditions leading to size…
Neurodegenerative diseases are driven by the accumulation of protein aggregates in the brain of affected individuals. The aggregation behaviour in vitro is well understood and driven by the equilibration of a super-saturated protein…
In cell membranes, proteins and lipids diffuse in a highly crowded and heterogeneous landscape, where aggregates and dense domains of proteins or lipids obstruct the path of diffusing molecules. In general, hindered motion gives rise to…
Several neurological disorders are associated with the aggregation of aberrant proteins, often localized in intracellular organelles such as the endoplasmic reticulum. Here we study protein aggregation kinetics by mean-field reactions and…
The qualitative behavior of a recently formulated ODE model for the dynamics of heterogenous aggregates is analyzed. Aggregates contain two types of particles, oligomers and cross-linkers. The motivation is a preparatory step of cellular…
The internal and external mechanical environment plays an important role in tumorogenesis. As a proxy of an avascular early state tumor, we use multicellular spheroids, a composite material made of cells, extracellular matrix and permeating…
Simulation plays a central role in scientific discovery. In many applications, the bottleneck is no longer running a simulator; it is choosing among large families of plausible simulators, each corresponding to different forward…
Membrane proteins often form dimers and higher-order oligomers whose stability and spatial organization depend sensitively on their lipid environment. To investigate the physical principles underlying this coupling, we employ a lattice…
We investigate the folding behavior of protein sequences by numerically studying all sequences with maximally compact lattice model through exhaustive enumeration. We get the prion-like behavior of protein folding. Individual proteins…
A simulation methodology for predicting the time-course of enzymatic digestions is described. The model is based solely on the enzyme's subsite architecture and concomitant binding energies. This allows subsite binding energies to be used…
The spatio-temporal organization of proteins and the associated morphological changes in membranes are of importance in cell signaling. Several mechanisms that promote the aggregation of proteins at low cell surface concentrations have been…
Neurodegenerative diseases are characterized by the accumulation of misfolded proteins and widespread disruptions in brain function. Computational modeling has advanced our understanding of these processes, but efforts have traditionally…
Aggregation of ubiquitinated cargo by oligomers of the protein p62 is an important preparatory step in cellular autophagy. In this work a mathematical model for the dynamics of these heterogeneous aggregates in the form of a system of…