相关论文: Lambda-ABF-OPES: Faster Convergence with High Accu…

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…

In adaptive-bias enhanced sampling methods, a bias potential is added to the system to drive transitions between metastable states. The bias potential is a function of a few collective variables and is gradually modified according to the…

We introduce an efficient and robust method to compute alchemical free energy differences, resulting from the application of multiple walker Adaptive Biasing Force (ABF) in conjunction with strongly damped Langevin $\lambda$-dynamics.…

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…

Free-energy-based adaptive biasing methods, such as Metadynamics, the Adaptive Biasing Force (ABF) and their variants, are enhanced sampling algorithms widely used in molecular simulations. Although their efficiency has been empirically…

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…

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…

The efficacy of drug treatments depends on how tightly small molecules bind to their target proteins. The rapid and accurate quantification of the strength of these interactions (as measured by binding affinity) is a grand challenge of…

Molecular simulations are playing an ever increasing role, finding applications in fields as varied as physics, chemistry, biology and material science. However, many phenomena of interest take place on time scales that are out of reach of…

We develop an efficient sampling and free energy calculation technique within the adaptive biasing potential (ABP) framework. By mollifying the density of states we obtain an approximate free energy and an adaptive bias potential that is…

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…

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…

We present convergence results for an adaptive algorithm to compute free energies, namely the adaptive biasing force (ABF) method. The free energy is the effective potential associated to a so-called reaction coordinate (RC). Computing free…

Free energy perturbation (FEP) is frequently used to evaluate the free energy change of a biological process, e.g. the drug binding free energy or the ligand solvation free energy. Due to the sampling inefficiency, FEP is often employed…

Flow and diffusion models achieve high-fidelity, high-resolution image synthesis, but often require many function evaluations (NFEs) at sampling time. Existing acceleration methods either require additional training through distillation or…

Ab initio molecular dynamics (AIMD) with hybrid density functionals and plane wave basis is computationally expensive due to the high computational cost of exact exchange energy evaluation. Recently, we proposed a strategy to combine…

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…

This paper presents an adaptive stochastic spectral embedding (ASSE) method to solve the probabilistic AC optimal power flow (AC-OPF), a critical aspect of power system operation. The proposed method can efficiently and accurately estimate…

Many models of interest in the natural and social sciences have no closed-form likelihood function, which means that they cannot be treated using the usual techniques of statistical inference. In the case where such models can be…

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…