SAMTI: Sampling Adaptive Thermodynamic Integration for Alchemical Free Energy Calculations.

ABSTRACT: Accurate and efficient calculation of alchemical free energies is a critical challenge in computational chemistry, frequently hindered by the inherent limitations of conventional thermodynamic integration (TI) methods. These limitations include poor phase-space overlap between discrete alchemical states, inefficient allocation of computational resources, and a fundamental time scale separation between alchemical transformations and molecular conformational sampling, which collectively lead to slow convergence and high statistical uncertainty. This work presents sampling adaptive thermodynamic integration (SAMTI), a unified computational framework designed to systematically overcome these challenges. SAMTI synergistically integrates four components: (1) serial tempering (ST) with a fine-gra

SUBMITTER: Lee TS 

PROVIDER: S-EPMC12746446 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature