2006/08/22 by Guha Jayachandran, Michael R. Shirts, Sanghyun Park +1 · 1 citation
Biochemistry, Genetics and Molecular Biology · Materials Science · Chemistry · #Protein Structure and Dynamics #Enzyme Structure and Function #Free energy perturbation #Docking (animal) #Computation #Molecular dynamics #Computer science #A priori and a posteriori #Exploit #Perturbation (astronomy) #Algorithm #Biological system #Statistical physics #Computational chemistry #Chemistry #Physics
paper · doi:10.1063/1.2221680
openalex publication_date 2006/08/22 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/11
We present a technique for biomolecular free energy calculations that exploits highly parallelized sampling to significantly reduce the time to results. The technique combines free energies for multiple, nonoverlapping configurational macrostates and is naturally suited to distributed computing. We describe a methodology that uses this technique with docking, molecular dynamics, and free energy perturbation to compute absolute free energies of binding quickly compared to previous methods. The method does not require a priori knowledge of the binding pose as long as the docking technique used can generate reasonable binding modes. We demonstrate the method on the protein FKBP12 and eight of its inhibitors.