相关论文: Development and large-scale benchmarks of a protei…

Alchemical binding free energy (BFE) calculations offer an efficient and thermodynamically rigorous approach to in silico binding affinity predictions. As a result of decades of methodological improvements and recent advances in computer…

Absolute Binding Free Energy (ABFE) methods are among the most accurate computational techniques for predicting protein-ligand binding affinities, but their utility is limited by the need for many simulations of alchemically modified…

Accurate prediction of protein-ligand binding affinities is crucial in drug discovery, particularly during hit-to-lead and lead optimization phases, however, limitations in ligand force fields continue to impact prediction accuracy. In this…

Free energy perturbation (FEP) is considered the gold-standard simulation method for estimating small molecule binding affinity, a quantity of vital importance to drug discovery. The accuracy of FEP critically depends on an accurate model…

Relative Binding Free Energy (RBFE) calculations are a cornerstone of rational hit-to-lead and lead optimization in modern drug discovery. However, the high computational cost and limited reliability in tackling large or complex molecular…

Protein-ligand binding affinity prediction is essential for drug discovery and toxicity assessment. While machine learning (ML) promises fast and accurate predictions, its progress is constrained by the availability of reliable data. In…

Accurately predicting protein-ligand binding free energies (BFEs) remains a central challenge in drug discovery, particularly because the most reliable methods, such as free energy perturbation (FEP), are computationally intensive and…

This letter gives results on improving protein-ligand binding affinity predictions based on molecular dynamics simulations using machine learning potentials with a hybrid neural network potential and molecular mechanics methodology…

The Alchemical Transfer Method (ATM) is herein validated against the relative binding free energies of a diverse set of protein-ligand complexes. We employed a streamlined setup workflow, a bespoke force field, and the AToM-OpenMM software…

Predicting the binding affinity between small molecules and target macromolecules while combining both speed and accuracy, is a cornerstone of modern computational drug discovery which is critical for accelerating therapeutic development.…

AlphaFold 3 (AF3), the latest version of protein structure prediction software, goes beyond its predecessors by predicting protein-protein complexes. It could revolutionize drug discovery and protein engineering, marking a major step…

Protein-ligand binding prediction is a fundamental problem in AI-driven drug discovery. Prior work focused on supervised learning methods using a large set of binding affinity data for small molecules, but it is hard to apply the same…

Advancements in AI for science unlocks capabilities for critical drug discovery tasks such as protein-ligand binding affinity prediction. However, current models overfit to existing oversimplified datasets that does not represent naturally…

The primary objective of most lead optimization campaigns is to enhance the binding affinity of ligands. For large molecules such as antibodies, identifying mutations that enhance antibody affinity is particularly challenging due to the…

The massively parallel computation of absolute binding free energy with a well-equilibrated system (MP-CAFEE) has been developed [H. Fujitani, Y. Tanida, M. Ito, G. Jayachandran, C. D. Snow, M. R. Shirts, E. J. Sorin, and V. S. Pande, J.…

The prediction of protein 3D structure from amino acid sequence is a computational grand challenge in biophysics, and plays a key role in robust protein structure prediction algorithms, from drug discovery to genome interpretation. The…

Accurate absolute binding free energy (ABFE) calculations can reduce the time and cost of identifying drug candidates from a diverse pool of molecules that may have been overlooked experimentally. These calculations typically employ…

We introduce the self-Relative Binding Free Energy (self-RBFE) approach to evaluate the intrinsic statistical variance of dual-topology alchemical binding free energy estimators. The self-RBFE is the relative binding free energy between a…

Decision-making under uncertainty in energy management is complicated by unknown parameters hindering optimal strategies, particularly in Battery Energy Storage System (BESS) operations. Predict-Then-Optimise (PTO) approaches treat…

We present an extension of Alchemical Transfer Method (ATM) for the estimation of relative binding free energies of molecular complexes applicable to conventional as well as scaffold-hopping alchemical transformations. The method, named…