Sunday, April 18, 2021

210424 Improved Methods for Sampling the Configurational Space of Flexible Biomolecules

Title:
Improved Methods for Sampling the Configurational Space of Flexible Biomolecules

Speaker:
徐瑋澤(Wei-Tse Hsu), Ph.D. student, University of Colorado Boulder

Time:
04/24 (Sat.) 8 pm PDT, 9 pm MDT, 10 pm CDT, 11 pm EDT
04/25 (Sun.) 5 am CEST, 11 am Taiwan
Time zone conversion tool

Keywords:
Computational biophysics, molecular dynamics, molecular dynamics, free energy calculations, advanced sampling methods, deep learning, biophysics


Abstract:
Molecular simulations, including molecular dynamics and Monte Carlo simulations, have been widely used to gain insights into the transformation processes of condensed matter,including phase transitions, chemical reactions, and conformational changes of biomolecules. However, the usefulness of classical molecular simulations is severely restricted by kinetic bottlenecks in systems with a rough free energy surface. Metastable states separated by numerous free energy barriers are far from each other in the phasespace and have no probability overlap, leading to prohibitive computational cost for computational sampling. To address this challenge, various advanced sampling methods have been developed in the past decades. These methods, such as replica exchange,expanded ensemble, and metadynamics, greatly accelerate configurational sampling by either modifying the underlying free energy surface along selected slow degrees of freedom or bridging the gap between metastable states with a series of intermediate states. In this study, we provide an overview of the most commonly used methods. In light of the limitations of the existing methods, we also propose a variation of metadynamics, where alchemical variables can be biased as an allowed collective variable.

No comments:

Post a Comment