We have carried out an extended reference set of explicit solvent molecular dynamics simulations (63 simulations with 8.4 μs of simulation data) of canonical A-RNA duplexes. Most of the simulations were done using the latest variant of the Cornell et al. AMBER RNA force field bsc0χ(OL3), while several other RNA force fields have been tested. The calculations show that the A-RNA helix compactness, described mainly by geometrical parameters inclination, base pair roll, and helical rise, is sequence-dependent. In the calculated set of structures, the inclination varies from 10° to 24°. On the basis of simulations with modified bases (inosine and 2,6-diaminopurine), we suggest that the sequence-dependence of purely canonical A-RNA double helix is caused by the steric shape of the base pairs, i.e., the van der Waals interactions. The electrostatic part of stacking does not appear to affect the A-RNA shape. Especially visible is the role of the minor groove amino group of purines. This resembles the so-called Dickerson-Calladine mechanical rules suggested three decades ago for the DNA double helices. We did not identify any long-living backbone substate in A-RNA double helices that would resemble, for example, the B-DNA BI/BII dynamics. The variability of the A-RNA compactness is due to mutual movements of the consecutive base pairs coupled with modest change of the glycosidic χ torsion. The simulations further show that the A-RNA compactness is modestly affected by the water model used, while the effect of ionic conditions, investigated in the range from net-neutral condition to ~0.8 M monovalent ion excess salt, is smaller.

• MeSH
• 2-aminopurin analogy a deriváty   chemie   MeSH
• inosin chemie   MeSH
• konformace nukleové kyseliny MeSH
• molekulární modely MeSH
• RNA chemie   MeSH
• rozpouštědla chemie   MeSH
• simulace molekulární dynamiky * MeSH
• soli chemie   MeSH
• voda chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 2-aminopurin MeSH
• 2,6-diaminopurine MeSH Prohlížeč
• inosin MeSH
• RNA MeSH
• rozpouštědla MeSH
• soli MeSH
• voda MeSH

We have developed an algorithm, "MOLE," for the rapid, fully automated location and characterization of molecular channels, tunnels, and pores. This algorithm has been made freely available on the Internet (http://mole.chemi.muni.cz/) and overcomes many of the shortcomings and limitations of the recently developed CAVER software. The core of our MOLE algorithm is a Dijkstra's path search algorithm, which is applied to a Voronoi mesh. Tests on a wide variety of biomolecular systems including gramicidine, acetylcholinesterase, cytochromes P450, potassium channels, DNA quadruplexes, ribozymes, and the large ribosomal subunit have demonstrated that the MOLE algorithm performs well. MOLE is thus a powerful tool for exploring large molecular channels, complex networks of channels, and molecular dynamics trajectories in which analysis of a large number of snapshots is required.

• MeSH
• algoritmy * MeSH
• databáze proteinů MeSH
• iontové kanály chemie   MeSH
• konformace proteinů MeSH
• krystalografie rentgenová MeSH
• molekulární modely MeSH
• proteiny chemie   MeSH
• software * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• iontové kanály MeSH
• proteiny MeSH

BACKGROUND: The main aim of this study was to develop and implement an algorithm for the rapid, accurate and automated identification of paths leading from buried protein clefts, pockets and cavities in dynamic and static protein structures to the outside solvent. RESULTS: The algorithm to perform a skeleton search was based on a reciprocal distance function grid that was developed and implemented for the CAVER program. The program identifies and visualizes routes from the interior of the protein to the bulk solvent. CAVER was primarily developed for proteins, but the algorithm is sufficiently robust to allow the analysis of any molecular system, including nucleic acids or inorganic material. Calculations can be performed using discrete structures from crystallographic analysis and NMR experiments as well as with trajectories from molecular dynamics simulations. The fully functional program is available as a stand-alone version and as plug-in for the molecular modeling program PyMol. Additionally, selected functions are accessible in an online version. CONCLUSION: The algorithm developed automatically finds the path from a starting point located within the interior of a protein. The algorithm is sufficiently rapid and robust to enable routine analysis of molecular dynamics trajectories containing thousands of snapshots. The algorithm is based on reciprocal metrics and provides an easy method to find a centerline, i.e. the spine, of complicated objects such as a protein tunnel. It can also be applied to many other molecules. CAVER is freely available from the web site http://loschmidt.chemi.muni.cz/caver/.

• MeSH
• algoritmy MeSH
• internet MeSH
• konformace proteinů MeSH
• krystalografie rentgenová metody   MeSH
• magnetická rezonanční spektroskopie MeSH
• počítačová simulace MeSH
• proteiny chemie   MeSH
• proteomika metody   MeSH
• Rhodococcus MeSH
• rozpouštědla chemie   MeSH
• sekundární struktura proteinů MeSH
• software MeSH
• Sphingomonas MeSH
• Xanthobacter MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• proteiny MeSH
• rozpouštědla MeSH