Related papers: Target search on a dynamic DNA molecule
DNA-interacting proteins have roles multiple processes, many operating as molecular machines which undergo dynamic metastable transitions to bring about their biological function. To fully understand this molecular heterogeneity, DNA and…
The most common gene regulation mechanism is when a protein binds to a regulatory sequence to change RNA transcription. However, these sequences are short relative to the genome length, so finding them poses a challenging search problem.…
We analyze velocity-jump process models of persistent search for a single target on a bounded domain. The searcher proceeds along ballistic trajectories and is absorbed upon collision with the target boundary. When reaching the domain…
The mechanical model based on beads and springs, which we recently proposed to study non-specific DNA-protein interactions [J. Chem. Phys. 130, 015103 (2009)], was improved by describing proteins as sets of interconnected beads instead of…
We propose a dynamical model for non-specific DNA-protein interaction, which is based on the 'bead-spring' model previously developed by other groups, and investigate its properties using Brownian Dynamics simulations. We show that the…
In bacteria, regulatory proteins search for a specific DNA binding target via "facilitated diffusion": a series of rounds of 3D diffusion in the cytoplasm, and 1D linear diffusion along the DNA contour. Using large scale Brownian dynamics…
We introduce a probabilistic model for protein sliding motion along DNA during the search of a target sequence. The model accounts for possible effects due to sequence-dependent interaction between the nonspecific DNA and the protein. As an…
This review examines intermittent target search strategies, which combine phases of slow motion, allowing the searcher to detect the target, and phases of fast motion during which targets cannot be detected. We first show that intermittent…
Much of the complexity observed in gene regulation originates from cooperative protein-DNA binding. While studies of the target search of proteins for their specific binding sites on the DNA have revealed design principles for the…
All living systems can function only far away from equilibrium, and for this reason chemical kinetic methods are critically important for uncovering the mechanisms of biological processes. Here we present a new theoretical method of…
Generating molecules that bind to specific proteins is an important but challenging task in drug discovery. Previous works usually generate atoms in an auto-regressive way, where element types and 3D coordinates of atoms are generated one…
We study how Cas9, a central component of the CRISPR/Cas9 system, searches for a target sequence on the DNA. We propose a model that includes as key ingredients 3D diffusion, 1D sliding along the DNA, and the effect of short binding…
We theoretically address minimal search strategies of active, self-propelled particles towards hidden targets in three-dimensional space. The particles can sense if a target is close, e.g., by detecting signaling molecules released by a…
The function of protein, RNA, and DNA is modulated by fast, dynamic exchanges between three-dimensional conformations. Conformational sampling of biomolecules with exact and nullspace inverse kinematics, using rotatable bonds as revolute…
Despite recent advances in protein-ligand structure prediction, deep learning methods remain limited in their ability to accurately predict binding affinities, particularly for novel protein targets dissimilar from the training set. In…
Molecular search phenomena are observed in a variety of chemical and biological systems. During the search the participating particles frequently move in complex inhomogeneous environments with random transitions between different dynamic…
Search problems at various scales involve a searcher, be it a molecule before reaction or a foraging animal, which performs an intermittent motion. Here we analyze a generic model based on such type of intermittent motion, in which the…
The endoplasmic reticulum (ER) is a network of sheet-like and tubular structures that spans much of a cell and contains molecules undergoing diffusive searches for targets, such as unfolded proteins searching for chaperones and…
We study the dynamics of a deterministic walk confined in a narrow two-dimensional space randomly filled with point-like targets. At each step, the walker visits the nearest target not previously visited. Complex dynamics is observed at…
The precision of biochemical signaling is limited by randomness in the diffusive arrival of molecules at their targets. For proteins binding to the specific sites on the DNA and regulating transcription, the ability of the proteins to…