Related papers: Ligand unbinding pathway and mechanism analysis as…

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…

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…

Studying the pathways of ligand-receptor binding is essential to understand the mechanism of target recognition by small molecules. The binding free energy and kinetics of protein-ligand complexes can be computed using molecular dynamics…

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…

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…

Prediction of protein-ligand binding affinity is a major goal in drug discovery. Generally, free energy gap is calculated between two states (e.g., ligand binding and unbinding). The energy gap implicitly includes the effects of changes in…

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…

The binding between proteins and ligands plays a crucial role in the realm of drug discovery. Previous deep learning approaches have shown promising results over traditional computationally intensive methods, but resulting in poor…

Ligand diffusion through proteins is a fundamental process governing biological signaling and enzymatic catalysis. The complex topology of protein tunnels results in difficulties with computing ligand escape pathways by standard molecular…

Protein-ligand modeling underpins computational drug discovery and molecular design. Existing protein-ligand benchmarks typically evaluate whether a protein and ligand interact and how strongly they bind, through tasks such as binary…

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,…

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…

Protein-ligand complex structures have been utilised to design benchmark machine learning methods that perform important tasks related to drug design such as receptor binding site detection, small molecule docking and binding affinity…

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…

Determining the complete set of ligands' binding/unbinding pathways is important for drug discovery and to rationally interpret mutation data. Here we have developed a metadynamics-based technique that addressed this issue and allows…

Protein-ligand binding is the process by which a small molecule (drug or inhibitor) attaches to a target protein. Binding affinity, which characterizes the strength of biomolecular interactions, is essential for tackling diverse challenges…

Protein-ligand binding complexes are ubiquitous and essential to life. Protein-ligand binding affinity prediction (PLA) quantifies the binding strength between ligands and proteins, providing crucial insights for discovering and designing…

Receptor-ligand interactions are essential for biological function and their binding strength is commonly explained in terms of static lock-and-key models based on molecular complementarity. However, detailed information of the full…

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…

Protein-ligand interactions are one of the fundamental types of molecular interactions in living systems. Ligands are small molecules that interact with protein molecules at specific regions on their surfaces called binding sites. Tasks…