Related papers: Automated Workflow for Absolute Binding Free Energ…
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…
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.…
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…
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…
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.…
Calculating relative free energies is a topic of substantial interest and has many applications including solvation and binding free energies, which are used in computational drug discovery. However, there remain the challenges of accuracy,…
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.…
We present a new method that combines alchemical transformation with physical pathway to accurately and efficiently compute the absolute binding free energy of receptor-ligand complex. Currently, the double decoupling method (DDM) and the…
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…
Exact exchange contributions are known to crucially affect electronic states, which in turn govern covalent bond formation and breaking in chemical species. Empirically averaging the exact exchange admixture over compositional degrees of…
Enhanced sampling and free energy calculation algorithms of the Thermodynamic Integration family (such as the Adaptive Biasing Force method, ABF) are not based on the direct computation of a free energy surface, but rather of its gradient.…
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…
We have recently discussed an algorithm to automatically generate auxiliary basis sets (ABSs) of the standard form for density fitting (DF) or resolution-of-the-identity (RI) calculations in a given atomic orbital basis set (OBS) of any…
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…
We present a simulation protocol that allows for efficient sampling of the degrees of freedom of a solute in explicit solvent. The protocol involves using a non-equilibrium umbrella sampling method, in this case the recently developed…
Performing high accuracy hybrid functional calculations for condensed matter systems containing a large number of atoms is at present computationally very demanding - when not out of reach - if high quality basis sets are used. We present a…
The primary limitation for the application of alchemical free energy methods to a wider variety of complex molecular systems is achieving reasonable sampling. Flexible binding complexes often have high free energy barriers, which require…
Absolute binding free energy (ABFE) calculations offer a theoretically rigorous approach for predicting protein--ligand binding affinities without the scaffold constraints of relative binding free energy (RBFE) perturbations. However, broad…
The unique electron deficiency of boron makes it challenging to determine the stable structures, leading to a wide variety of forms. In this work, we introduce a statistical model based on grand canonical ensemble theory that incorporates…
One reason that free energy difference calculations are notoriously difficult in molecular systems is due to insufficient conformational overlap, or similarity, between the two states or systems of interest. The degree of overlap is…