Continuous Tempering Molecular Dynamics: A Deterministic Approach to Simulated Tempering

Continuous tempering molecular dynamics (CTMD) generalizes simulated tempering (ST) to a continuous temperature space. Opposed to ST the CTMD equations of motion are fully deterministic and feature a conserved quantity that can be used to validate the simulation. Three variants of CTMD are discussed and compared by means of a simple test system. The implementation features of the most stable and simplest variant CTMD-Uin the program package Iphigenieare described. Two applications – alanine dipeptide (Ac-Ala-NHMe) in explicit water and octa-alanine (Ac-(Ala)8-NHMe) simulated in a dielectric continuum – demonstrate the functionality of CTMD-U. Furthermore, they serve to evaluate its sampling efficiency. Here, CTMD-Uoutperforms ST by 35% and replica exchange even by 75%.