相关论文: Sampling of conformational ensemble for virtual sc…

Structure-based virtual screening aims to identify high-affinity ligands by estimating binding free energies between proteins and small molecules. However, the conformational flexibility of both proteins and ligands challenges conventional…

The rapid evolution of molecular dynamics (MD) methods, including machine-learned dynamics, has outpaced the development of standardized tools for method validation. Objective comparison between simulation approaches is often hindered by…

Molecular docking is a cornerstone of drug discovery, relying on high-resolution ligand-bound structures to achieve accurate predictions. However, obtaining these structures is often costly and time-intensive, limiting their availability.…

We report the performance of our newly introduced Ensemble Docking with Enhanced sampling of pocket Shape (EDES) protocol coupled to a template-based algorithm to generate near-native ligand conformations in the 2019 iteration of the Grand…

Protein function does not solely depend on structure but often relies on dynamical transitions between distinct conformations. Despite this fact, our ability to characterize or predict protein dynamics is substantially less developed…

Protein function frequently involves conformational changes with large amplitude on timescales which are difficult and computationally expensive to access using molecular dynamics. In this paper, we report on the combination of three…

Structure-based virtual screening is an important tool in early stage drug discovery that scores the interactions between a target protein and candidate ligands. As virtual libraries continue to grow (in excess of $10^8$ molecules), so too…

Due to the time-scale limitations of all-atom simulation of proteins, there has been substantial interest in coarse-grained approaches. Some methods, like "Resolution Exchange," [E. Lyman et al., Phys. Rev. Lett. 96, 028105 (2006)] can…

Understanding protein conformational dynamics is essential for elucidating biological function but remains challenging due to the wide range of timescales and the complexity of collective motions. Enhanced sampling methods overcome…

All-atom molecular dynamics (MD) computer simulations are a valuable tool for characterizing the conformational ensembles of intrinsically disordered proteins (IDPs). IDP conformational ensembles are highly heterogeneous and contain…

We have earlier reported the iMOLSDOCK technique to perform induced-fit peptide-protein docking. iMOLSDOCK uses the mutually orthogonal Latin squares (MOLS) technique to sample the conformation and the docking pose of the small molecule…

Sampling useful three-dimensional molecular structures along with their most favorable conformations is a key challenge in drug discovery. Current state-of-the-art 3D de-novo design flow matching or diffusion-based models are limited to…

Deep generative models have achieved tremendous success in designing novel drug molecules in recent years. A new thread of works have shown the great potential in advancing the specificity and success rate of in silico drug design by…

We present a novel machine learning approach to understanding conformation dynamics of biomolecules. The approach combines kernel-based techniques that are popular in the machine learning community with transfer operator theory for…

The biomolecules in and around a living cell -- proteins, nucleic acids, lipids, carbohydrates -- continuously sample myriad conformational states that are thermally accessible at physiological temperatures. Simultaneously, a given…

The bottleneck in enhanced sampling lies in finding collective variables (CVs) that can effectively accelerate protein conformational changes. True reaction coordinates (tRCs) that can predict the committor are considered the optimal CVs,…

Simulations of biological macromolecules play an important role in understanding the physical basis of a number of complex processes such as protein folding. Even with increasing computational power and evolution of specialized…

Excitement at the prospect of using data-driven generative models to sample configurational ensembles of biomolecular systems stems from the extraordinary success of these models on a diverse set of high-dimensional sampling tasks. Unlike…

Significant progress in computer hardware and software have enabled molecular dynamics (MD) simulations to model complex biological phenomena such as protein folding. However, enabling MD simulations to access biologically relevant…

We propose a benchmark to study surrogate model accuracy for protein-ligand docking. We share a dataset consisting of 200 million 3D complex structures and 2D structure scores across a consistent set of 13 million "in-stock" molecules over…