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Here we present a single-cell-based model of cell-cell interactions in a growing yeast colony. We examine the influence of multiple factors on the colony morphology and switch to a foraging growth behavior. We find that the cell-growth inhibition by neighboring cells along with polar division growth patterns are the most significant factors driving the exploratory behavior of a colony.
Bone morphogenetic proteins (BMPs) are pleiotropic secreted proteins, structurally related to transforming growth factor (TGF)-beta and activins. BMPs play pivotal roles in the regulation of embryonic lung development and branching of airways and have recently been considered to influence inflammatory processes in adults due to their chemotactic activity on fibroblasts, myocytes, and inflammatory
We identify a mutation (D262N) in the erythroid-affiliated transcriptional repressor GFI1B, in an acute myeloid leukemia (AML) patient with antecedent myelodysplastic syndrome (MDS). The GFI1B-D262N mutant functionally antagonizes the transcriptional activity of wild-type GFI1B. GFI1B-D262N promoted myelomonocytic versus erythroid output from primary human hematopoietic precursors and enhanced cel
Recent design experiments have demonstrated that some proteins can switch their folds in response to a small number of point mutations either directly, in a single mutational step, or via intermediate bistable sequences, which populate two different folds simultaneously. Here we explore the hypothesis that bistable intermediates are more common in switches between structurally similar folds while
A major challenge in the development of peptide-based vaccines is finding the right immunogenic element, with efficient and long-lasting immunization effects, from large potential targets encoded by pathogen genomes. Computer models are convenient tools for scanning pathogen genomes to preselect candidate immunogenic peptides for experimental validation. Current methods predict many false positive
Plants continue to grow and generate new organs in symmetric patterns throughout their lives. This development requires an interconnected regulation of genes, hormones, and anisotropic growth, which in part is guided by environmental cues. Recently, several studies have used a combination of experiments and mathematical modeling to elucidate the mechanisms behind different growth and molecular pat
We present a new software framework for Markov chain Monte Carlo sampling for simulation, prediction, and inference of protein structure. The software package contains implementations of recent advances in Monte Carlo methodology, such as efficient local updates and sampling from probabilistic models of local protein structure. These models form a probabilistic alternative to the widely used fragm
The binding of short disordered peptide stretches to globular protein domains is important for a wide range of cellular processes, including signal transduction, protein transport, and immune response. The often promiscuous nature of these interactions and the conformational flexibility of the peptide chain, sometimes even when bound, make the binding specificity of this type of protein interactio
Coupled folding-binding is central to the function of many intrinsically disordered proteins, yet not fully understood. With a continuous three-letter protein model, we explore the free-energy landscape of pairs of interacting sequences and how it is impacted by 1), variations in the binding mechanism; and 2), the addition of disordered flanks to the binding region. In particular, we focus on two
We study analytically the tracer particle mobility in single-file systems with distributed friction constants. Our system serves as a prototype for nonequilibrium, heterogeneous, strongly interacting Brownian systems. The long time dynamics for such a single-file setup belongs to the same universality class as the Rouse model with dissimilar beads. The friction constants are drawn from a density r
Recent experiments uncovered a mutational pathway between two proteins, along which a single mutation causes a switch in fold. Searching for such paths between real proteins remains, despite this achievement, a true challenge. Here, we analyze fold switching in the minimalistic hydrophobic/polar model on a square lattice. For this analysis, we generate a comprehensive sequence-structure database f
Protein dynamics play a crucial role in function, catalytic activity, and pathogenesis. Consequently, there is great interest in computational methods that probe the conformational fluctuations of a protein. However, molecular dynamics simulations are computationally costly and therefore are often limited to comparatively short timescales. TYPHON is a probabilistic method to explore the conformati
In this study we derive a single-particle equation of motion, from first principles, starting out with a microscopic description of a tracer particle in a one-dimensional many-particle system with a general two-body interaction potential. Using a harmonization technique, we show that the resulting dynamical equation belongs to the class of fractional Langevin equations, a stochastic framework whic
The Hybrid Monte Carlo method offers a rigorous and potentially efficient approach to the simulation of dense systems, by combining numerical integration of Newton's equations of motion with a Metropolis accept-or-reject step. The Metropolis step corrects for sampling errors caused by the discretization of the equations of motion. The integration is usually performed using a uniform step size. Her
We demonstrate how nanofluidic channels can be used as a tool to rapidly determine the number and sizes of plasmids in bacterial isolates. Each step can be automated at low cost, opening up opportunities for general use in microbiology labs.
