Recent Developments in Linear Interaction Energy Based Binding Free Energy Calculations

Free energy calculations and ligand binding.

Dark Energy: Recent Developments *

A six parameter cosmological model, involving a vacuum energy density that is extremely tiny compared to fundamental particle physics scales, describes a large body of increasingly accurate astronomical data. In a first part of this brief review we summarize the current situation, emphasizing recent progress. An almost infinitesimal vacuum energy is only the simplest candidate for a cosmologica...

Using the fast fourier transform in binding free energy calculations.

According to implicit ligand theory, the standard binding free energy is an exponential average of the binding potential of mean force (BPMF), an exponential average of the interaction energy between the unbound ligand ensemble and a rigid receptor. Here, we use the fast Fourier transform (FFT) to efficiently evaluate BPMFs by calculating interaction energies when rigid ligand configurations fr...

Is Ring Breaking Feasible in Relative Binding Free Energy Calculations?

Our interest is relative binding free energy (RBFE) calculations based on molecular simulations. These are promising tools for lead optimization in drug discovery, computing changes in binding free energy due to modifications of a lead compound. However, in the "alchemical" framework for RBFE calculations, some types of mutations have the potential to introduce error into the computed binding f...

Towards accurate free energy calculations in ligand protein-binding studies.

Cells contain a multitude of different chemical reaction paths running simultaneously and quite independently next to each other. This amazing feat is enabled by molecular recognition, the ability of biomolecules to form stable and specific complexes with each other and with their substrates. A better understanding of this process, i.e. of the kinetics, structures and thermodynamic properties o...