scholarly journals Generating Reservoir Conformations for Replica Exchange through the Use of the Conformational Space Annealing Method

2013 ◽  
Vol 9 (2) ◽  
pp. 1115-1124 ◽  
Author(s):  
Asim Okur ◽  
Benjamin T. Miller ◽  
Keehyoung Joo ◽  
Jooyoung Lee ◽  
Bernard R. Brooks
Keyword(s):  
Conformational Space ◽  
Replica Exchange ◽  
Annealing Method

UNRES-Dock—protein–protein and peptide–protein docking by coarse-grained replica-exchange MD simulations

2020 ◽  
Author(s):  
Paweł Krupa ◽  
Agnieszka S Karczyńska ◽  
Magdalena A Mozolewska ◽  
Adam Liwo ◽  
Cezary Czaplewski
Keyword(s):  
Protein Complexes ◽  
Md Simulations ◽  
Protein Docking ◽  
Conformational Space ◽  
Coarse Grained ◽  
Supplementary Information ◽  
Replica Exchange ◽  
Variable Degree ◽  
Single Chain ◽  
Simulation Speed

Abstract Motivation The majority of the proteins in living organisms occur as homo- or hetero-multimeric structures. Although there are many tools to predict the structures of single-chain proteins or protein complexes with small ligands, peptide–protein and protein–protein docking is more challenging. In this work, we utilized multiplexed replica-exchange molecular dynamics (MREMD) simulations with the physics-based heavily coarse-grained UNRES model, which provides more than a 1000-fold simulation speed-up compared with all-atom approaches to predict structures of protein complexes. Results We present a new protein–protein and peptide–protein docking functionality of the UNRES package, which includes a variable degree of conformational flexibility. UNRES-Dock protocol was tested on a set of 55 complexes with size from 43 to 587 amino-acid residues, showing that structures of the complexes can be predicted with good quality, if the sampling of the conformational space is sufficient, especially for flexible peptide–protein systems. The developed automatized protocol has been implemented in the standalone UNRES package and in the UNRES server. Availability and implementation UNRES server: http://unres-server.chem.ug.edu.pl; UNRES package and data used in testing of UNRES-Dock: http://unres.pl. Supplementary information Supplementary data are available at Bioinformatics online.

Conformational space search of Neuromedin C using replica exchange molecular dynamics and molecular dynamics

2010 ◽  
Vol 17 (3) ◽  
pp. 174-183 ◽  
Author(s):  
Parul Sharma ◽  
Parvesh Singh ◽  
Krishna Bisetty ◽  
Alex Rodriguez ◽  
Juan J. Perez
Keyword(s):  
Molecular Dynamics ◽  
Conformational Space ◽  
Replica Exchange ◽  
Replica Exchange Molecular Dynamics

MOLECULAR DYNAMICS SIMULATIONS OF DNA DIMERS BASED ON REPLICA-EXCHANGE UMBRELLA SAMPLING I: TEST OF SAMPLING EFFICIENCY

2005 ◽  
Vol 04 (02) ◽  
pp. 411-432 ◽  
Author(s):  
KATSUMI MURATA ◽  
YUJI SUGITA ◽  
YUKO OKAMOTO
Keyword(s):  
Molecular Dynamics ◽  
Time Series ◽  
Molecular Dynamics Simulations ◽  
Umbrella Sampling ◽  
Conformational Space ◽  
Replica Exchange ◽  
Time Step ◽  
Torsion Angles ◽  
Dynamics Simulations ◽  
Phase Angles

In order to elucidate the stacking-unstacking process of DNA dimers, we have performed molecular dynamics simulations based on replica-exchange umbrella sampling (REUS), which is one of powerful conformational sampling techniques. We studied four DNA dimers composed of the adenine and thymine bases in both the 5′ and the 3′ positions (dApdA, dApdT, dTpdA, and dTpdT). We examined the time series of the distance between the glycosidic nitrogen atoms, root-mean-square deviations from A-DNA and B-DNA, various backbone and glycosidic torsion angles, and the pseudorotation phase angles as functions of the simulation time step. All these time series imply that the present simulation has indeed sampled a very wide conformational space. The results for the backbone and glycosidic torsion angles and pseudorotation phase angles imply that B-DNA structures are the dominant motif of the stacked dimers, while a small population of A-DNA also exists in the stacked states.

scholarly journals Effects of Force Fields on the Conformational and Dynamic Properties of Amyloid β(1-40) Dimer Explored by Replica Exchange Molecular Dynamics Simulations

2017 ◽  
Author(s):  
Charles R. Watts ◽  
Andrew Gregory ◽  
Cole Frisbie ◽  
Sándor Lovas
Keyword(s):  
Molecular Dynamics ◽  
Force Field ◽  
Force Fields ◽  
Dynamic Properties ◽  
Amyloid Β ◽  
Md Simulations ◽  
Conformational Space ◽  
Random Coil ◽  
Replica Exchange ◽  
Β Sheet

AbstractAlzheimer’s disease is histologically marked by fibrils of Amyloid beta (Aβ) peptide within the extracellular matrix. Fibrils themselves are benign compared to the cytotoxicity of the oligomers and pre-fibrillary aggregates. The conformational space and structural ensembles of Aβ peptides and their oligomers in solution are inherently disordered and proven to be challenging to study. Optimum force field selection for molecular dynamics (MD) simulations and the biophysical relevance of results are still unknown. We compared the conformational space of the Aβ(1–40) dimers by 300 ns replica exchange MD simulations at physiological temperature (310 K) using: the AMBER-ff99sb-ILDN, AMBER-ff99sb*-ILDN, AMBER-ff99sb-NMR, and CHARMM22* force fields. Statistical comparisons of simulation results to experimental data and previously published simulations utilizing the CHARMM22* and CHARMM36 force fields were performed. All force fields yield sampled ensembles of conformations with collision cross sectional areas for the dimer that are statistically significantly larger than experimental results. All force fields, with the exception of AMBER-ff99sb-ILDN (8.8±6.4%) and CHARMM36 (2.7±4.2%), tend to overestimate the α-helical content compared to experimental CD (5.3±5.2%). Using the AMBER-ff99sb-NMR force field resulted in the greatest degree of variance (41.3±12.9%). Except for the AMBER-ff99sb-NMR force field, the others tended to under estimate the expected amount of β-sheet and over estimate the amount of turn/bend/random coil conformations. All force fields, with the exception AMBER-ff99sb-NMR, reproduce a theoretically expected β-sheet-turn-β-sheet conformational motif, however, only the CHARMM22* and CHARMM36 force fields yield results compatible with collapse of the central and C-terminal hydrophobic cores from residues 17-21 and 30-36. Although analyses of essential subspace sampling showed only minor variations between force fields, secondary structures of lowest energy conformers are different.

Improved conformational space annealing method to treat β-structure with the UNRES force-field and to enhance scalability of parallel implementation

Polymer ◽  
2004 ◽  
Vol 45 (2) ◽  
pp. 677-686 ◽  
Author(s):  
Cezary Czaplewski ◽  
Adam Liwo ◽  
Jarosław Pillardy ◽  
Stanisław Ołdziej ◽  
Harold A. Scheraga
Keyword(s):  
Force Field ◽  
Parallel Implementation ◽  
Conformational Space ◽  
Annealing Method

scholarly journals Enhanced Conformational Sampling of Nanobody CDR H3 Loop by Generalized Replica-Exchange with Solute Tempering

Life ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1428
Author(s):  
Ren Higashida ◽  
Yasuhiro Matsunaga
Keyword(s):  
Potential Energy ◽  
Lessons Learned ◽  
Solute Molecule ◽  
Conformational Space ◽  
Replica Exchange ◽  
Conformational Sampling ◽  
Loop Modeling ◽  
Variable Domains ◽  
Scaling Parameters ◽  
Potential Energy Term

The variable domains of heavy-chain antibodies, known as nanobodies, are potential substitutes for IgG antibodies. They have similar affinities to antigens as antibodies, but are more heat resistant. Their small size allows us to exploit computational approaches for structural modeling or design. Here, we investigate the applicability of an enhanced sampling method, a generalized replica-exchange with solute tempering (gREST) for sampling CDR-H3 loop structures of nanobodies. In the conventional replica-exchange methods, temperatures of only a whole system or scaling parameters of a solute molecule are selected for temperature or parameter exchange. In gREST, we can flexibly select a part of a solute molecule and a part of the potential energy terms as a parameter exchange region. We selected the CDR-H3 loop and investigated which potential energy term should be selected for the efficient sampling of the loop structures. We found that the gREST with dihedral terms can explore a global conformational space, but the relaxation to the global equilibrium is slow. On the other hand, gREST with all the potential energy terms can sample the equilibrium distribution, but the structural exploration is slower than with dihedral terms. The lessons learned from this study can be applied to future studies of loop modeling.

Computational Investigations of the Transmembrane Italian-Mutant (E22K) 3A\(\beta_{11 - 40}\) in Aqueous Solution

2018 ◽  
Vol 28 (3) ◽  
pp. 265 ◽  
Author(s):  
Son Tung Ngo
Keyword(s):  
Structural Changes ◽  
Replica Exchange ◽  
Aβ Oligomers ◽  
Replica Exchange Molecular Dynamics ◽  
Charged Residue ◽  
Intermolecular Contacts ◽  
Structural Details ◽  
Positively Charged ◽  
Dynamic Fluctuation ◽  
Good Agreement

The Amyloid beta (Aβ) oligomers are characterized as critical cytotoxic materials in Alzheimer’s disease (AD) pathogenesis. Structural details of transmembrane oligomers are inevitably necessary to design/search potential inhibitor due to treat AD. However, the experimental detections for structural modify of low-order Aβ oligomers are precluded due to the extremely dynamic fluctuation of the oligomers. In this project, the transmembrane Italian-mutant (E22K) 3Aβ11-40 (tmE22K 3Aβ11-40) was extensively investigated upon the temperature replica exchange molecular dynamics (REMD) simulations. The structural changes of the trimer when replacing the negative charged residue E22 by a positively charged residue K were monitored over simulation intervals. The oligomer size was turned to be larger and the increase of β-content was recorded. The momentous gain of intermolecular contacts with DPPC molecules implies that tmE22K 3Aβ11-40 easier self-inserts into the membrane than the WT one. Furthermore, the tighter interaction between constituting monomers was indicated implying that the E22K mutation probably enhances the Aβ fibril formation. The results are in good agreement with experiments that E22K amyloid is self-aggregate faster than the WT form. Details information of tmE22K trimer structure and kinetics probably yield the understanding of AD mechanism.

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