TY - JOUR
T1 - Enhanced sampling techniques in molecular dynamics simulations of biological systems
AU - Bernardi, Rafael C.
AU - Melo, Marcelo C.R.
AU - Schulten, Klaus
N1 - Funding Information:
The authors gratefully acknowledge funding from the Energy Biosciences Institute (EBI, 231 UCB BP 2014OO4J01 ). This work was supported by grants from the National Institutes of Health (NIH, 9P41GM104601 ) and the National Science Foundation (NSF, MCB-1157615 to KS). Simulations made use of the NCSA Blue Waters sustained-petascale supercomputer as part of the general allocations (Simulations of Cellulosomal Subunits: Components of a Molecular Machinery for Depolymerization of Feedstock for Production of Second Generation Biofuels) and the NERSC/Edison supercomputer as part of the Department of Energy (DoE) 2014 ASCR Leadership Computing Challenge.
PY - 2015/5
Y1 - 2015/5
N2 - Background: Molecular dynamics has emerged as an important research methodology covering systems to the level of millions of atoms. However, insufficient sampling often limits its application. The limitation is due to rough energy landscapes, with many local minima separated by high-energy barriers, which govern the biomolecular motion. Scope of review: In the past few decades methods have been developed that address the sampling problem, such as replica-exchange molecular dynamics, metadynamics and simulated annealing. Here we present an overview over theses sampling methods in an attempt to shed light on which should be selected depending on the type of system property studied. Major conclusions: Enhanced sampling methods have been employed for a broad range of biological systems and the choice of a suitable method is connected to biological and physical characteristics of the system, in particular system size. While metadynamics and replica-exchange molecular dynamics are the most adopted sampling methods to study biomolecular dynamics, simulated annealing is well suited to characterize very flexible systems. The use of annealing methods for a long time was restricted to simulation of small proteins; however, a variant of the method, generalized simulated annealing, can be employed at a relatively low computational cost to large macromolecular complexes. General significance: Molecular dynamics trajectories frequently do not reach all relevant conformational substates, for example those connected with biological function, a problem that can be addressed by employing enhanced sampling algorithms. This article is part of a Special Issue entitled Recent developments of molecular dynamics.
AB - Background: Molecular dynamics has emerged as an important research methodology covering systems to the level of millions of atoms. However, insufficient sampling often limits its application. The limitation is due to rough energy landscapes, with many local minima separated by high-energy barriers, which govern the biomolecular motion. Scope of review: In the past few decades methods have been developed that address the sampling problem, such as replica-exchange molecular dynamics, metadynamics and simulated annealing. Here we present an overview over theses sampling methods in an attempt to shed light on which should be selected depending on the type of system property studied. Major conclusions: Enhanced sampling methods have been employed for a broad range of biological systems and the choice of a suitable method is connected to biological and physical characteristics of the system, in particular system size. While metadynamics and replica-exchange molecular dynamics are the most adopted sampling methods to study biomolecular dynamics, simulated annealing is well suited to characterize very flexible systems. The use of annealing methods for a long time was restricted to simulation of small proteins; however, a variant of the method, generalized simulated annealing, can be employed at a relatively low computational cost to large macromolecular complexes. General significance: Molecular dynamics trajectories frequently do not reach all relevant conformational substates, for example those connected with biological function, a problem that can be addressed by employing enhanced sampling algorithms. This article is part of a Special Issue entitled Recent developments of molecular dynamics.
KW - Cellulosome
KW - Enhanced sampling
KW - Generalized simulated annealing
KW - Metadynamics
KW - Molecular dynamics
KW - Replica-exchange molecular dynamics
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U2 - 10.1016/j.bbagen.2014.10.019
DO - 10.1016/j.bbagen.2014.10.019
M3 - Review article
C2 - 25450171
AN - SCOPUS:84923166744
VL - 1850
SP - 872
EP - 877
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
SN - 0304-4165
IS - 5
ER -