FEP+ Pose Builder Methodology for Simulations

This white paper presents the FEP+ Pose Builder, a methodological advancement designed to enhance the efficiency and productivity of FEP simulations. It addresses the challenges associated with traditional FEP+ pose setup, which is often time-consuming, resource-intensive, and complicated by steric clashes and system complexity. The FEP+ Pose Builder automates the generation of FEP-ready poses through a four-stage protocol that includes ligand preparation, reference identification, ligand alignment, and clash resolution. Each stage is detailed, explaining how the tool prepares ligands, identifies optimal references, aligns ligands based on user input, and resolves steric clashes. The paper also benchmarks the performance of poses generated by the FEP+ Pose Builder against manually curated poses, demonstrating comparable results in a significantly reduced timeframe. By standardizing the creation of reliable FEP-ready inputs, this tool aims to maximize accessibility and cost-effectiveness in molecular simulations, thereby facilitating advancements in computational chemistry.