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The structure, dynamics, and thermal stability of the structurally similar 14-mer RNA hairpins uCACGg and cUUCGg are studied by using replica-exchange molecular dynamics simulations. The two RNA hairpins exhibited similar structures at room temperature, but the UUCG loop was found to be more flexible than the CACG loop.

Adopting trialanine as a paradigm of a small peptide, a comprehensive comparison of six popular force fields is presented, including the recent versions of AMBER, CHARMM, GROMOS, and OPLS models. For all force fields under consideration a 20ns long MD simulation is performed to study in detail the structure and conformational dynamics of the solvated peptide.

A technique for the photoisomerization of retinal rhodopsin using a vibronically coupled electronic two-state system is described.

The time-resolved femtosecond spectroscopy in conjunction with nonequilibrium molecular dynamics (MD) simulations was used to study the energy transport in a short helical peptide in chloroform solution. A simple harmonic model of heat transport adopted on the bases of results showed that the heat diffusivity decreased significantly at temperatures initially reached by high-energy excitation.

The conformational structure and dynamics of trialanine in water are studied with the help of a molecular dynamics (MD) study. The MD study reveals that the conformational structures and dynamics show good overall agreement with experimental data.

Adopting extensive molecular dynamicssimulations of villin headpieceprotein (HP35) by Shaw and co-workers, a detailed theoretical analysisof the folding of HP35 is presented. The approach is based on therecently proposed most probable pathalgorithm whichidentifies the metastable states of the system, combined with dynamicalcoring of these states in order to obtain a consistent Markov statemodel. The method facilitates the construction of a dendrogram associatedwith the folding free-energy landscape of HP35, which reveals a hierarchicalfunnel structure and shows that the native state is rather a kinetictrap than a network hub. The energy landscape of HP35 consists ofthe entropic unfolded basin U, where the prestructuringof the protein takes place, the intermediate basin I, which is connected to Uvia the rate-limiting U→ Itransition state reflectingthe formation of helix-1, and the native basin N,containing a state close to the NMR structure and a native-like statethat exhibits enhanced fluctuations of helix-3. The model is in linewith recent experimental observations that the intermediate and nativestates differ mostly in their dynamics (locked vs unlocked states).Employing dihedral angle principal component analysis, subdiffusivemotion on a multidimensional free-energy surface is found. [ABSTRACT FROM AUTHOR]

Given nonstationary data from molecular dynamics simulations, a Markovian Langevin model is constructed that aims to reproduce the time evolution of the underlying process. While at equilibrium the free energy landscape is sampled, nonequilibrium processes can be associated with a biased energy landscape, which accounts for finite sampling effects and external driving. When the data-driven Langevin equation (dLE) approach [ Phys . Rev . Lett . 2015 , 115 , 050602] is extended to the modeling of nonequilibrium processes, an efficient way to calculate multidimensional Langevin fields is outlined. The dLE is shown to correctly account for various nonequilibrium processes, including the enforced dissociation of sodium chloride in water, the pressure-jump induced nucleation of a liquid of hard spheres, and the conformational dynamics of a helical peptide sampled from nonstationary short trajectories.

A local perturbation of a protein may lead to functional changes at some distal site. An example is the PDZ2 domain of human tyrosine phosphatase 1E, which shows an allosteric transition upon binding to a peptide ligand. Recently Buchli et al. presented a time-resolved study of this transition by covalently linking an azobenzene photoswitch across the binding groove and using a femtosecond laser pulse that triggers the cis-trans photoisomerization of azobenzene. To aid the interpretation of these experiments, in this work seven microsecond runs of all-atom molecular dynamics simulations each for the wild-type PDZ2 in the ligand-bound and -free state, as well as the photoswitchable protein (PDZ2S) in the cis and trans states of the photoswitch, in explicit water were conducted. First the theoretical model is validated by recalculating the available NMR data from the simulations. By comparing the results for PDZ2 and PDZ2S, it is analyzed to what extent the photoswitch indeed mimics the free-bound transition. A detailed description of the conformational rearrangement following the cis-trans photoisomerization of PDZ2S reveals a series of photoinduced structural changes that propagate from the anchor residues of the photoswitch via intermediate secondary structure segments to the C-terminus of PDZ2S. The changes of the conformational distribution of the C-terminal region is considered as the distal response of the isolated allosteric protein.

Employing nonequilibrium molecular dynamics (MD) simulations and transient infrared (IR) spectroscopy, a joint theoretical/experimental study on a water-soluble photoswitchable octapeptide designed by Renner et al. [Biopolymers 2002, 63, 382] is presented. The simulations predict the cooling of the hot photoproducts on a time scale of 7 ps and complex conformational rearrangements ranging from a few picoseconds to several nanoseconds. The experiments yield a dominant fast relaxation time of 5 ps, which is identified as the cooling time of the peptide in water and also accounts for initial conformational changes of the system. Moreover, a weaker component of 300 ps is found, which reflects the overall conformational relaxation of the system. The virtues and the limitations of the joint MD/IR approach to describe biomolecular conformational rearrangements are discussed.