相关论文: Estimation of Protein-Ligand Unbinding Kinetics Us…

The interaction lifetimes between condensate-forming biomolecules can dictate both the specificity of the condensate-forming species as well as the fluidity and exchange dynamics of these condensates. Using a heuristic modeling approach, we…

Analysis of bond rupture data from single-molecule force spectroscopy experiments commonly relies on the strong assumption that the bond dissociation process is irreversible. However, with increased spatiotemporal resolution of instruments…

In drug discovery, molecular dynamics (MD) simulation for protein-ligand binding provides a powerful tool for predicting binding affinities, estimating transport properties, and exploring pocket sites. There has been a long history of…

Accurate prediction of protein-ligand binding affinity is crucial for rapid and efficient drug development. Recently, the importance of predicting binding affinity has led to increased attention on research that models the three-dimensional…

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…

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…

The adhesion of biological membranes is mediated by the binding of membrane-anchored receptor and ligand proteins. Central questions are how the binding kinetics of these proteins is affected by the membranes and by the membrane anchoring…

The unbinding process of a protein-ligand complex of major biological interest was investigated by means of a computational approach at atomistic classical mechanical level. An energy minimisation-based technique was used to determine the…

This study introduces a novel computational approach based on ratchet-and-pawl molecular dynamics (rMD) for accurately estimating ligand dissociation kinetics in protein-ligand complexes. By integrating Kramers' theory with Bell's equation,…

We propose a computational method to quantitatively evaluate the systematic uncertainties that arise from undetectable sources in biological measurements using live-cell imaging techniques. We then demonstrate this method in measuring…

Protein binding and function often involves conformational changes. Advanced NMR experiments indicate that these conformational changes can occur in the absence of ligand molecules (or with bound ligands), and that the ligands may 'select'…

The protein-ligand residence time, tau, influences molecular function in biological networks and has been recognized as an important determinant of drug efficacy. To predict tau, computational methods must overcome the problem that tau…

We develop a formalism for single molecule dynamic force spectroscopy to map the energy landscape of protein-protein complex ($P_1$$P_2$). The joint distribution $P(\tau_1,\tau_2)$ of unbinding lifetimes $\tau_1$ and $\tau_2$ measurable in…

Most widely used ligand docking methods assume a rigid protein structure. This leads to problems when the structure of the target protein deforms upon ligand binding. In particular, the ligand's true binding pose is often scored very…

The development of machine-learning (ML) potentials offers significant accuracy improvements compared to molecular mechanics (MM) because of the inclusion of quantum-mechanical effects in molecular interactions. However, ML simulations are…

Characterization of protein energy landscape and conformational ensembles is important for understanding mechanisms of protein folding and function. We studied ensembles of bound and unbound conformations of six proteins to explore their…

Myosin motors are fundamental biological actuators, powering diverse mechanical tasks in eukaryotic cells via ATP hydrolysis. Recent work revealed that myosin's velocity-dependent detachment rate can bridge actomyosin dynamics to macroscale…

Rebinding of dissociated ligands from cell surface proteins can confound quantitative measurements of dissociation rates important for characterizing the affinity of binding interactions. This can be true also for in vitro techniques such…

A coarse-grained molecular simulation approach originally developed for entangled polymeric liquids is extended to model the mechanical behavior of long-fiber networks. The model, based on the slip-link picture of chain entanglements,…

Specific binding of proteins to DNA is one of the most common ways in which gene expression is controlled. Although general rules for the DNA-protein recognition can be derived, the ambiguous and complex nature of this mechanism precludes a…