Abstract
Molecular dynamics simulation using enhanced sampling methods is one of the powerful computational tools used to explore protein conformations and free energy landscapes. Enhanced sampling methods often employ either an increase in temperature or a flattening of the potential energy surface to rapidly sample phase space, and a corresponding reweighting algorithm is used to recover the Boltzmann statistics. However, potential energies of complex biomolecules usually involve large fluctuations on a magnitude of hundreds of kcal/mol despite minimal structural changes during simulation. This leads to noisy reweighting statistics and complicates the obtainment of accurate final results. To overcome this common issue in enhanced conformational sampling, we propose a scaled molecular dynamics method, which modifies the biomolecular potential energy surface and employs a reweighting scheme based on configurational populations. Statistical mechanical theory is applied to derive the reweighting formula, and the canonical ensemble of simulated structures is recovered accordingly. Test simulations on alanine dipeptide and the fast folding polypeptide Chignolin exhibit sufficiently enhanced conformational sampling and accurate recovery of free energy surfaces and thermodynamic properties. The results are comparable to long conventional molecular dynamics simulations and exhibit better recovery of canonical statistics over methods which employ a potential energy term in reweighting.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.