An Improved Free Energy Perturbation FEP+ Sampling Protocol for Flexible Ligand-Binding Domains

Enhanced Ligand Sampling for Relative Protein–Ligand Binding Free Energy Calculations

Free energy calculations are used to study how strongly potential drug molecules interact with their target receptors. The accuracy of these calculations depends on the accuracy of the molecular dynamics (MD) force field as well as proper sampling of the major conformations of each molecule. However, proper sampling of ligand conformations can be difficult when there are large barriers separati...

Free energy calculations and ligand binding.

An Improved Junction-Based Directional Routing Protocol (IJDRP) for VANETs

Vehicular Ad-Hoc Networks (VANETs) is a novel technology that has recently emerged and due to its swift changing topology and high mobility nature, it has become problematic to design an efficient routing protocol in VANETs’ amongst both moving and stationary units. Also, the existing routing algorithms are not very effective to satisfy all requirements of VANETs. This paper explores the need o...

Multi-Layer Free Energy Perturbation

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 together with computationally expensive enhanced sampling methods. Here we show that this sampling inefficiency, which stems from not accounting for the environ...

Sampling and energy evaluation challenges in ligand binding protein design

The steroid hormone 17α-hydroxylprogesterone (17-OHP) is a biomarker for congenital adrenal hyperplasia and hence there is considerable interest in development of sensors for this compound. We used computational protein design to generate protein models with binding sites for 17-OHP containing an extended, nonpolar, shape-complementary binding pocket for the four-ring core of the compound, and ...