2 research outputs found
Explicit Water Models Affect the Specific Solvation and Dynamics of Unfolded Peptides While the Conformational Behavior and Flexibility of Folded Peptides Remain Intact
Conventional molecular dynamics simulations on 50 ns to 1 μs time scales were used to study the effects of explicit solvent models on the conformational behavior and solvation of two oligopeptide solutes: α-helical EK-peptide (14 amino acids) and a β-hairpin chignolin (10 amino acids). The widely used AMBER force fields (ff99, ff99SB, and ff03) were combined with four of the most commonly used explicit solvent models (TIP3P, TIP4P, TIP5P, and SPC/E). Significant differences in the specific solvation of chignolin among the studied water models were identified. Chignolin was highly solvated in TIP5P, whereas reduced specific solvation was found in the TIP4P, SPC/E, and TIP3P models for kinetic, thermodynamic, and both kinetic and thermodynamic reasons, respectively. The differences in specific solvation did not influence the dynamics of structured parts of the folded peptide. However, substantial differences between TIP5P and the other models were observed in the dynamics of unfolded chignolin, stability of salt bridges, and specific solvation of the backbone carbonyls of EK-peptide. Thus, we conclude that the choice of water model may affect the dynamics of flexible parts of proteins that are solvent-exposed. On the other hand, all water models should perform similarly for well-structured folded protein regions. The merits of the TIP3P model include its high and overestimated mobility, which accelerates simulation processes and thus effectively increases sampling
Molecular Mechanism of preQ<sub>1</sub> Riboswitch Action: A Molecular Dynamics Study
Riboswitches often occur in the 5′-untranslated
regions
of bacterial mRNA where they regulate gene expression. The preQ<sub>1</sub> riboswitch controls the biosynthesis of a hypermodified nucleoside
queuosine in response to binding the queuosine metabolic intermediate.
Structures of the ligand-bound and ligand-free states of the preQ<sub>1</sub> riboswitch from <i>Thermoanaerobacter tengcongensis</i> were determined recently by X-ray crystallography. We used multiple,
microsecond-long molecular dynamics simulations (29 μs in total)
to characterize the structural dynamics of preQ<sub>1</sub> riboswitches
in both states. We observed different stabilities of the stem in the
bound and free states, resulting in different accessibilities of the
ribosome-binding site. These differences are related to different
stacking interactions between nucleotides of the stem and the associated
loop, which itself adopts different conformations in the bound and
free states. We suggest that the loop not only serves to bind preQ<sub>1</sub> but also transmits information about ligand binding from
the ligand-binding pocket to the stem, which has implications for
mRNA accessibility to the ribosome. We explain functional results
obscured by a high salt crystallization medium and help to refine
regions of disordered electron density, which demonstrates the predictive
power of our approach. Besides investigating the functional dynamics
of the riboswitch, we have also utilized this unique small folded
RNA system for analysis of performance of the RNA force field on the
μs time scale. The latest AMBER parmbsc0χ<sub>OL3</sub> RNA force field is capable of providing stable trajectories of the
folded molecule on the μs time scale. On the other hand, force
fields that are not properly balanced lead to significant structural
perturbations on the sub-μs time scale, which could easily lead
to inappropriate interpretation of the simulation data