State-Function Based Free Energy Correction (SFC)

Overview

The State-Function Based Free Energy Correction (SFC) algorithm is designed to improve the accuracy of relative binding free energy calculations. It utilizes state function properties to correct errors in pairwise free energy differences without requiring cycle identification, ensuring thermodynamic consistency across the entire network of molecular transformations.

Features

• Naturally satisfies thermodynamic cycle consistency.
• Fast computation suitable for large molecular networks, applicable to large-scale lead compound optimization based on FEP-RBFE calculations.
• Supports using estimated errors of calculated ddG values as weights for optimization.

Installation

1. Clone this repository:

git clone git@github.com:ZheLi-Lab/State-Function-based-free-energy-correction-SFC-.git
cd sfc

2. Install required dependencies:

pip install -r requirements.txt

Usage

Basic Usage (based on least squares optimization)

Run the SFC algorithm on your input file:

python main.py -f example/n20_c0.10_u0.50_edges.csv -r 1 -e 0.0 -p yes --no_header

Parameters:

• -f, --file: Input file containing pairwise energy data
• -r, --ref: Reference molecule (default: first molecule in data)
• -e, --energy: Reference energy value
• -p, --pair: if yes: print detailed results of the pair ddG, no: only molecule energies
• --no_header: Input file has no header row

Matrix-Based Usage (matrix mode)

To use the SFC algorithm with the matrix-based solver (instead of the optimizer), specify the --mode matrix option:

python main.py -f example/n20_c0.10_u0.50_edges.csv -r 1 -e 0.0 --mode matrix --no_header

Parameters:

• --mode matrix: Use the matrix method for free energy correction (recommended for ultra-large-scale datasets)
• Other parameters are the same as in the basic usage

Input File Format

The input file should be a CSV file with the following columns:

Molecule1 Molecule2 ddG [Error]

• Molecule1, Molecule2: Molecule pair identifiers
• ddG: Free energy difference between the molecules
• Error: (Optional) Uncertainty in the free energy difference

Output Files

The program generates several output files in the same directory as the input file:

• *_pair.txt: Corrected pairwise ΔΔG
• *_node.txt: Corrected ΔG
• *_time.txt: Execution time and statistics

Reference

Liu, R.; Lai, Y.; Yao, Y.; Huang, W.; Zhong, Y.; Luo, H.-B.; Li, Z. State Function-Based Correction: A Simple and Efficient Free-Energy Correction Algorithm for Large-Scale Relative Binding Free-Energy Calculations. J. Phys. Chem. Lett. https://doi.org/10.1021/acs.jpclett.5c01119.