biostudies-literatureHayes RLDivision of ChemistryNational Institute of General Medical SciencesNIGMS NIH HHS6799-6807https://www.ebi.ac.uk/biostudies/studies/S-EPMC8626863biostudies-literatureUnknown17(11)There is an accelerating interest in practical applications of alchemical free energy methods to problems in protein design, constant pH simulations, and especially computer-aided drug design. In the present paper, we describe a basic lambda dynamics engine (BLaDE) that enables alchemical free energy simulations, including multisite λ dynamics (MSλD) simulations, on graphical processor units (GPUs). We find that BLaDE is 5 to 8 times faster than the current GPU implementation of MSλD-based free energy calculations in CHARMM. We also demonstrate that BLaDE running standard molecular dynamics attains a performance competitive with and sometimes exceeding that of the highly optimized OpenMM GPU code. BLaDE is available as a standalone program and through an API in CHARMM.Journal of chemical theory and computationBLaDE: A Basic Lambda Dynamics Engine for GPU-Accelerated Molecular Dynamics Free Energy Calculations.PMC8626863GM37554R35 GM130587GM130587R01 GM037554CHE 1506273Buckner JBrooks CLHayes RLfalseBLaDE: A Basic Lambda Dynamics Engine for GPU-Accelerated Molecular Dynamics Free Energy Calculations.There is an accelerating interest in practical applications of alchemical free energy methods to problems in protein design, constant pH simulations, and especially computer-aided drug design. In the present paper, we describe a basic lambda dynamics engine (BLaDE) that enables alchemical free energy simulations, including multisite λ dynamics (MSλD) simulations, on graphical processor units (GPUs). We find that BLaDE is 5 to 8 times faster than the current GPU implementation of MSλD-based free energy calculations in CHARMM. We also demonstrate that BLaDE running standard molecular dynamics attains a performance competitive with and sometimes exceeding that of the highly optimized OpenMM GPU code. BLaDE is available as a standalone program and through an API in CHARMM.2021-01-01T00:00:00Z2021 Nov2025-04-26T16:27:02.113Z2025-04-06T15:13:34.834ZS-EPMC86268633470904610.1021/acs.jctc.1c00833