相关论文: maze: Heterogeneous Ligand Unbinding along Transie…

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…

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…

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…

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…

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…

Large parallel gains in the development of both computational resources as well as sampling methods have now made it possible to simulate dissociation events in ligand-protein complexes with all--atom resolution. Such encouraging progress,…

Path optimization methods have been widely used and highly successful for the analysis of chemical reactions. Yet, they can fail to capture intrinsically multidimensional features of potential energy surfaces (PES). We introduce the nudged…

Here we propose the Reweighted Autoencoded Variational Bayes for Enhanced Sampling (RAVE) method, a new iterative scheme that uses the deep learning framework of variational autoencoders to enhance sampling in molecular simulations. RAVE…

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…

Finding and sampling multiple reaction channels for molecular transitions remains an important challenge in physical chemistry. Here we show that the weighted ensemble (WE) path sampling method can readily sample multiple channels. In a…

Most existing random walk based network embedding methods often follow only one of two principles, homophily or structural equivalence. In real world networks, however, nodes exhibit a mixture of homophily and structural equivalence, which…

In multi-resolution simulations, different system components are simultaneously modelled at different levels of resolution, these being smoothly coupled together. In the case of enzyme systems, computationally expensive atomistic detail is…

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 assembly of proteins in membranes plays a key role in many crucial cellular pathways. Despite their importance, characterizing transmembrane assembly remains challenging for experiments and simulations. Equilibrium molecular dynamics…

Molecular dynamics (MD) simulation is widely used to study protein conformations and dynamics. However, conventional simulation suffers from being trapped in some local energy minima that are hard to escape. Thus, most computational time is…

The dissociation of ligands from proteins and other biomacromolecules occurs over a wide range of timescales. For most pharmaceutically relevant inhibitors, these timescales are far beyond those that are accessible by conventional molecular…

A plethora of protein language models have been released in recent years. Yet comparatively little work has addressed how to best sample from them to optimize desired biological properties. We fill this gap by proposing a flexible,…

We present a molecular simulation method to simultaneously find multiple transition pathways, and their associated free-energy profiles. The scheme extends path-metadynamics (PMD) [Phys. Rev. Lett. 109, 020601 (2012)] with multiple paths…

We present a method to sample reactive pathways via biased molecular dynamics simulations in trajectory space. We show that the use of enhanced sampling techniques enables unconstrained exploration of multiple reaction routes. Time…

Developing effective representations of protein structures is essential for advancing protein science, particularly for protein generative modeling. Current approaches often grapple with the complexities of the SE(3) manifold, rely on…