Sampling Performance of Multiple Independent Molecular Dynamics Simulations of an RNA Aptamer

Yan, Shuting
Peck, Jason M.
İlgü, Müslüm
Nilsen-Hamilton, Marit
Lamm, Monica H.
Using multiple independent simulations instead of one long simulation has been shown to improve the sampling performance attained with the molecular dynamics (MD) simulation method. However, it is generally not known how long each independent simulation should be, how many independent simulations should be used, or to what extent either of these factors affects the overall sampling performance achieved for a given system. The goal of the present study was to assess the sampling performance of multiple independent MD simulations, where each independent simulation begins from a different initial molecular conformation. For this purpose, we used an RNA aptamer that is 25 nucleotides long as a case study. The initial conformations of the aptamer are derived from six de novo predicted 3D structures. Each of the six de novo predicted structures is energy minimized in solution and equilibrated with MD simulations at high temperature. Ten conformations from these six high-temperature equilibration runs are selected as initial conformations for further simulations at ambient temperature. In total, we conducted 60 independent MD simulations, each with a duration of 100 ns, to study the conformation and dynamics of the aptamer. For each group of 10 independent simulations that originated from a particular de novo predicted structure, we evaluated the potential energy distribution of the RNA and used recurrence quantification analysis to examine the sampling of RNA conformational transitions. To assess the impact of starting from different de novo predicted structures, we computed the density of structure projection on principal components to compare the regions sampled by the different groups of ten independent simulations. The recurrence rate and dependence of initial conformation among the groups were also compared. We stress the necessity of using different initial configurations as simulation starting points by showing long simulations from different initial structures suffer from being trapped in different states. Finally, we summarized the sampling efficiency for the complete set of 60 independent simulations and determined regions of under-sampling on the potential energy landscape. The results suggest that conducting multiple independent simulations using a diverse set of de novo predicted structures is a promising approach to achieve sufficient sampling. This approach avoids undesirable outcomes, such as the problem of the RNA aptamer being trapped in a local minimum. For others wishing to conduct multiple independent simulations, the analysis protocol presented in this study is a guide for examining overall sampling and determining if more simulations are necessary for sufficient sampling.


Direct numerical simulation of pipe flow using a solenoidal spectral method
Tugluk, Ozan; Tarman, Işık Hakan (2012-05-01)
In this study, a numerical method based on solenoidal basis functions, for the simulation of incompressible flow through a circular-cylindrical pipe, is presented. The solenoidal bases utilized in the study are formulated using the Legendre polynomials. Legendre polynomials are favorable, both for the form of the basis functions and for the inner product integrals arising from the Galerkin-type projection used. The projection is performed onto the dual solenoidal bases, eliminating the pressure variable, si...
Comparison of methods for estimating carbonaceous BOD parameters
Uludag-Demirer, S; Demirer, Göksel Niyazi; Bowers, AR (Informa UK Limited, 2001-08-01)
The performance of seven different methods (Differential, Fujimoto, Thomas, Graphical, Integral, Log-Difference, and Nonlinear Regression) for estimating first-stage, carbonaceous biochemical oxygen demand (CBOD), curve parameters, namely k and L-0 were compared using synthetic data generated by Monte Carlo simulation technique. The comparison of the methods was made based on their efficiency in retrieving the original values of k and L-0 which were selected to generate the synthetic data. In the first part...
Semi-Bayesian Inference of Time Series Chain Graphical Models in Biological Networks
Farnoudkia, Hajar; Purutçuoğlu Gazi, Vilda (null; 2018-09-20)
The construction of biological networks via time-course datasets can be performed both deterministic models such as ordinary differential equations and stochastic models such as diffusion approximation. Between these two branches, the former has wider application since more data can be available. In this study, we particularly deal with the probabilistic approaches for the steady-state or deterministic description of the biological systems when the systems are observed though time. Hence, we consider time s...
Design and performance analysis of a pump-turbine system using computational fluid dynamics
Yıldız, Mehmet; Albayrak, Kahraman; Çelebioğlu, Kutay; Department of Mechanical Engineering (2011)
In this thesis, a parametric methodology is investigated to design a Pump-Turbine system using Computational Fluid Dynamics ( CFD ). The parts of Pump-Turbine are created parametrically according to the experience curves and theoretical design methods. Then, these parts are modified to obtain 500 kW turbine working as a pump with 28.15 meters head. The final design of Pump-Turbine parts are obtained by adjusting parameters according to the results of the CFD simulations. The designed parts of the Pump-Turbi...
Phonon dispersions and elastic constants of disordered Pd-Ni alloys
Kart, SO; Tomak, Mehmet; Cagin, T (Elsevier BV, 2005-01-31)
Phonon frequencies of Pd-Ni alloys are calculated by molecular dynamics (MD) simulation. Lattice dynamical properties computed from Sutton-Chen (SC) and quantum Sutton-Chen (Q-SC) potentials as a function of temperature are compared with each other. We present all interatomic force constants up to the 8th nearest-neighbor shell obtained by using the calculated potential. Elastic constants evaluated by two methods are consistent with each other. The transferability of the potential is also tested. The result...
Citation Formats
S. Yan, J. M. Peck, M. İlgü, M. Nilsen-Hamilton, and M. H. Lamm, “Sampling Performance of Multiple Independent Molecular Dynamics Simulations of an RNA Aptamer,” ACS OMEGA, pp. 20187–20201, 2020, Accessed: 00, 2020. [Online]. Available: