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Updated: Aug 24, 2026

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
Exploring the protein folding free energy landscape: coupling replica exchange method with P3ME/RESPA algorithm
1Computational Biology Center, IBM Thomas J. Watson Research Center, Yorktown Heights, NY 10598, USA. ruhongz@us.ibm.com
Abstract:
A highly parallel replica exchange method (REM) that couples with a newly developed molecular dynamics algorithm particle-particle particle-mesh Ewald (P3ME)/RESPA has been proposed for efficient sampling of protein folding free energy landscape. The algorithm is then applied to two separate protein systems, beta-hairpin and a designed protein Trp-cage. The all-atom OPLSAA force field with an explicit solvent model is used for both protein folding simulations. Up to 64 replicas of solvated protein systems are simulated in parallel over a wide range of temperatures. The combined trajectories in temperature and configurational space allow a replica to overcome free energy barriers present at low temperatures. These large scale simulations reveal detailed results on folding mechanisms, intermediate state structures, thermodynamic properties and the temperature dependences for both protein systems.
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