相关论文: Heterogeneous and rate-dependent streptavidin-biot…
Protein-ligand interactions are crucial for a wide range of physiological processes. Many cellular functions result in these non-covalent `bonds' being mechanically strained, and this can be integral to proper cellular function. Broadly,…
We probe the dynamic strength of multiple biotin-streptavidin adhesion bonds under linear loading using the biomembrane force probe setup for dynamic force spectroscopy. Measured rupture force histograms are compared to results from a…
Protein-ligand (un)binding simulations are a recent focus of biased molecular dynamics simulations. Such binding and unbinding can occur via different pathways in and out of a binding site. We here present a theoretical framework how to…
A key factor influencing a drug's efficacy is its residence time in the binding pocket of the host protein. Using atomistic computer simulation to predict this residence time and the associated dissociation process is a desirable but…
Understanding the dynamics of biomolecular complexes, e.g., of protein-ligand (un)binding, requires the understanding of paths such systems take between metastable states. In MD simulation data, paths are usually not observable per se, but…
We here report on non-equilibrium targeted Molecular Dynamics simulations as tool for the estimation of protein-ligand unbinding kinetics. Correlating simulations with experimental data from SPR kinetics measurements and X-ray…
Coarse-graining of fully atomistic molecular dynamics simulations is a long-standing goal in order to allow the description of processes occurring on biologically relevant timescales. For example, the prediction of pathways, rates and…
Rebinding kinetics of molecular ligands plays a critical role in biomachinery, from regulatory networks to protein transcription, and is also a key factor for designing drugs and high-precision biosensors.In this study, we investigate…
Searching for reaction pathways describing rare events in large systems presents a long-standing challenge in chemistry and physics. Incorrectly computed reaction pathways result in the degeneracy of microscopic configurations and inability…
Molecular motors walk along filaments until they detach stochastically with a force-dependent unbinding rate. Here, we show that this unbinding rate can be obtained from the analysis of experimental data of molecular motors moving in…
We present two methods to reveal protein-ligand unbinding mechanisms in biased unbinding simulations by clustering trajectories into ensembles representing unbinding paths. The first approach is based on a contact principal component…
Ligand-receptor binding and unbinding are fundamental biomolecular processes and particularly essential to drug efficacy. Environmental water fluctuations, however, impact the corresponding thermodynamics and kinetics and thereby challenge…
Understanding the differentiation, a biological process from a multipotent stem or progenitor state to a mature cell is critically important. We develop a theoretical framework to quantify the underlying potential landscape and biological…
We examined theory for force-induced unbinding on a two-dimensional free energy surface where the internal dynamics of biomolecules is coupled with the rupture process under constant tension f. We show that only if the transition state…
Cytoskeletal networks of biopolymers are cross-linked by a variety of proteins. Experiments have shown that dynamic cross-linking with physiological linker proteins leads to complex stress relaxation and enables network flow at long times.…
Retinoic acid receptor (RAR) is a ligand-dependent transcription factor that regulates the expression of genes involved in cell growth, differentiation, and development. Binding of the retinoic acid hormone to RAR is accompanied by…
The process of ligand-protein unbinding is crucial in biophysics. Water is an essential part of any biological system and yet, many aspects of its role remain elusive. Here, we simulate with state-of-the-art enhanced sampling techniques the…
Bistability is a major mechanism for cellular decision making and usually results from positive feedback in biochemical control systems. Here we show theoretically that bistability between unbound and bound states of adhesion clusters…
The dynamics of peptide-protein binding and unbinding of a variant of the RNase S system has been investigated. To initiate the process, a photoswitchable azobenzene moiety has been covalently linked to the S-peptide, thereby switching its…
In this paper we study a simple stochastic version of the Hopfield-Ninio kinetic proofreading model. The model is characterized by means of two parameters, the unbinding time, which depends on the binding energy between a ligand and a…