RED-E-Function-Based Equilibrium Parameter Finder: Finding the Best Restraint Parameters in Absolute Binding Free Energy Calculations.

Free energy perturbation (FEP)-based absolute binding free energy (ABFE) calculations have emerged as a powerful tool for the accurate prediction of ligand-protein binding affinities in drug discovery. The restraint addition is crucial in FEP-ABFE calculations; however, due to the non-orthogonal couplings between the restrained degrees of freedom, it typically requires numerous λ windows to ensure the phase-space overlap during restraint addition. This study introduces the RED-E-function-based equilibrium parameter finder (REPF), a novel method that relies on harmonic restraints to optimize the equilibrium values in restraints, enhancing phase-space overlap and improving the convergence of the restraint addition.

Convergence-Adaptive Roundtrip Method Enables Rapid and Accurate FEP Calculations.

The free energy perturbation (FEP) method is a powerful technique for accurate binding free energy calculations, which is crucial for identifying potent ligands with a high affinity in drug discovery. However, the widespread application of FEP is limited by the high computational cost required to achieve equilibrium sampling and the challenges in obtaining converged predictions. In this study, we present the convergence-adaptive roundtrip (CAR) method, which is an enhanced adaptive sampling approach, to address the key challenges in FEP calculations, including the precision-efficiency tradeoff, sampling efficiency, and convergence assessment.

An Improved Magnetic Field Method to Locate the Grounding Conductor.

The location of the grounding grid conductors is critical for performing corrosion diagnosis and maintenance work. An improved magnetic field differential method to locate the unknown grounding grid based on truncation errors and the round-off errors analysis is presented in this paper. It was proven that a different order of the magnetic field derivative can be used to determine the position of the grounding conductor according to the peak value of the derivative.