On easy implementation of a variant of the replica exchange with solute tempering in GROMACS

To reduce the number of replicas required in the conventional replica exchange method for huge systems, recently the replica exchange with solute tempering (REST) method was proposed. Here we showed that a variant of REST realized by rescaling the force-field parameters can be performed with GROMACS 4 without changing the code. We tested the variant REST for alanine dipeptide and an N-terminal peptide from p53 confirming its performance nearly equal to the original REST.     

Ergodicity and model quality in template‐restrained canonical and temperature/Hamiltonian replica exchange coarse‐grained molecular dynamics simulations of proteins

Molecular simulations restrained to single or multiple templates are commonly used in protein‐structure modeling. However, the restraints introduce additional barriers, thus impairing the ergodicity of simulations, which can affect the quality of the resulting models. In this work, the effect of restraint types and simulation schemes on ergodicity and model quality was investigated by performing template‐restrained canonical molecular dynamics (MD), multiplexed replica‐exchange molecular dynamics, and Hamiltonian replica exchange molecular dynamics (HREMD) simulations with the coarse‐grained UNRES force field on nine selected proteins, with pseudo‐harmonic log‐Gaussian (unbounded) or Lorentzian (bounded) restraint functions. The best ergodicity was exhibited by HREMD. It has been found that non‐ergodicity does not affect model quality if good templates are used to generate restraints. However, when poor‐quality restraints not covering the entire protein are used, the improved ergodicity of HREMD can lead to significantly improved protein models. © 2017 Wiley Periodicals, Inc.     

Dynamical van der Waals Model of Glassy Behavior

A model fluid system whose intermolecular forces consist of the short range part characterizing usual stable fluid and the long range part of Kac-type is considered. When the ratio of the force ranges is large enough, the system can be described by regarding the system having only short range interactions as a reference fluid treated as a continuum, on which long range forces acting among tiny fluid elements are superimposed. We discuss the glassy behavior of this model relating it to the mode coupling theory and using real replica theory. These theories lead to the two equations for non-ergodicity parameter which are totally different from each other. We argue that our model can be a basis for examining nature of the drastic approximations entering derivations of the mode coupling equations. We further explore the possibility of developing the dynamical real replica approach for our model system with the hope of providing a framework to cope with different time scales characterizing complex glassy behavior.     

多重交织抽样消除光电成像系统中的高阶残余频谱

光电成像系统的抽样过程引起图像频谱分布在频谱空间无限重复，即使抽样过程满足系统的Ｎｙｑｕｉｓｔ条件，即无频谱混叠，但在重建过程中，如果电子滤波的频率响应范围较宽，不能对高阶频谱项截止，它对高阶重复的频谱项的衰减所产生的残余频谱会在重建图像中产生假响应。本文提出用同一图像进行多重交织抽样的方法来消除重建过程中的高阶残余频谱，同时具有较好图像恢复的效果。在理论上用光学传递函数方法证明了有关的结论。     

Repeated‐annealing sampling combined with multicanonical algorithm for conformational sampling of bio‐molecules

A novel conformational sampling method (repeated‐annealing sampling method) is proposed to execute an efficient conformational sampling at a reasonable computational cost. In the method, a molecular dynamics simulation is done with repeating an elemental process. An elemental process consists of four subprocesses: high‐temperature run, annealing, room‐temperature run, and fast heating. The sampling is done automatically according to a temperature‐control schedule. The room‐temperature run is treated with the multicanonical algorithm, and the other subprocesses are done with the conventional molecular dynamics algorithm. The method, differing from the generalized ensemble methods recently developed, is not warrantable to give the canonical ensemble because of the nonphysical process in the annealing. However, we observed that the slower the annealing and the longer the high‐temperature run, the closer the sampled conformations to those of the canonical ensemble. A test was performed with tri‐N‐acetyl‐D ‐glucosamine in vacuo, and the results were compared with those from the conventional multicanonical simulation. Not only the reweighted canonical distribution function but also the energy landscape were in good agreement with those from the conventional multicanonical simulation. The potential of mean force also showed a fairly good agreement with that from the conventional multicanonical simulation in the room‐temperature region. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1098–1106, 2001     

Calculation of the relative free energy of oxidation of azurin at pH 5 and pH 9

Free energy calculations are described for the small copper‐containing redox protein Azurin from Pseudomonas aeruginosa. A thermodynamic cycle connecting the reduced and oxidized states at pH 5 and pH 9 is considered, allowing for an assessment of convergence in terms of hysteresis and cycle closure. Previously published thermodynamic integration (TI) data is compared to Hamiltonian replica exchange TI (RE‐TI) simulations using different simulation setups. The effects of varying simulation length, initial structure, position restraints on particular atoms, and the strength of temperature coupling are studied. Although the overall simulation times are too short to observe an experimentally described peptide plane rotation, it is found that RE‐TI simulations do stimulate the distribution of conformational changes over the relevant values of the TI coupling parameter λ. This results in significantly improved values for hysteresis and cycle closure when compared to regular TI. © 2012 Wiley Periodicals, Inc.     

<Emphasis Type="Italic">p</Emphasis>-Adic Pseudodifferential Operators and Analytic Continuation of Replica Matrices

We consider the procedure for analytic continuation of the replica matrix. We formulate a particular form of this procedure in which the analytic continuation is defined by a sequence of maps. Using this definition, we construct a solution that breaks the Parisi replica symmetry and find the corresponding p-adic pseudodifferential operator. __________ Translated from Teoreticheskaya i Matematicheskaya Fizika, Vol. 144, No. 2, pp. 336–341, August, 2005     

Reparameterizations of the χ Torsion and Lennard‐Jones σ Parameters Improve the Conformational Characteristics of Modified Uridines

The currently available force field parameters for modified RNA residues in AMBER show significant deviations in conformational properties from experimental observations. The examination of the transferability of the recently revised torsion parameters revealed that there was an overall improvement in the conformational properties for some of the modifications but the improvements were still insufficient in describing the sugar pucker preferences (J. Chem. Inf. Model. 2014, 54, 1129–1142). Here, we report an approach for the development and fine tuning of the AMBER force field parameters for 2‐thiouridine, 4‐thiouridine, and pseudouridine with diverse conformational preferences. The χ torsion parameters were reparameterized at the individual nucleoside level. The effect of combining the revised γ torsion parameter and modifying the Lennard‐Jones σ parameters were also tested by directly comparing the conformational preferences obtained from our extensive molecular dynamics simulations with those from experimental observations. © 2016 Wiley Periodicals, Inc.     

A novel strategy to determine protein structures using exclusively residual dipolar coupling

Recent advances in NMR techniques to measure anisotropic spin interactions such as residual dipolar coupling (RDC) have provided better insights into protein structure as well as dynamics. Exploitation of RDC, however, still remains challenging because its successful application requires a reasonable starting model. Using the singular value decomposition method, we have recently developed an RDC restraint potential to optimally extract orientational information from RDC without the prerequisite of any structural information. In the present study, its efficacy is further illustrated by folding a beta-hairpin and alpha-helix of protein G from extended conformations with RDC restraints alone by employing the replica exchange torsion angle molecular dynamics (REX-TAMD) technique. Subsequently, the entire structure of protein G has been determined accurately using the developed fragment superposition method (FRAGSUM). In FRAGSUM, each overlapping fragments (10 amino acids long) is first folded individually by REX-TAMD, and then the common amino acids are superimposed to determine the entire structure. Because FRAGSUM does not require any additional information besides RDC, it offers a new strategy for de novo structure determination using exclusively RDC.     

Alchemical Grid Dock (AlGDock): Binding Free Energy Calculations between Flexible Ligands and Rigid Receptors

Alchemical Grid Dock (AlGDock) is open-source software designed to compute the binding potential of mean force—the binding free energy between a flexible ligand and a rigid receptor—for a small organic ligand and a biological macromolecule. Multiple BPMFs can be used to rigorously compute binding affinities between flexible partners. AlGDock uses replica exchange between thermodynamic states at different temperatures and receptor–ligand interaction strengths. Receptor–ligand interaction energies are represented by interpolating precomputed grids. Thermodynamic states are adaptively initialized and adjusted on-the-fly to maintain adequate replica exchange rates. In demonstrative calculations, when the bound ligand is treated as fully solvated, AlGDock estimates BPMFs with a precision within 4 kT in 65% and within 8 kT for 91% of systems. It correctly identifies the native binding pose in 83% of simulations. Performance is sometimes limited by subtle differences in the important configuration space of sampled and targeted thermodynamic states. © 2019 Wiley Periodicals, Inc.