Molecular Dynamics Simulations Investigate The Structure And Function Of Several Proteins

In recent years, with the development of the information technology, moleculardynamics simulation has become an important means for investigate the interrelationbetween the structure and function of the Biological macromolecules. This paperanalyzes the interrelation between the structure and function of the several proteins bymolecular dynamics simulations. These systems are the following three parts:1. Molecular dynamics simulations of the thermal stability of tteRBP and ecRBPMolecular dynamics simulations were performed for investigating the thermalstability of the extremely thermophilic tteRBP and the mesophilic homologous ecRBPwhich are very similar in structure. The simulations for the two proteins were carriedout under the room temperature (300K) and the optimal activity temperature (tteRBP375K and ecRBP329K), respectively. The comparative analyses of the trajectoriesshow that the two proteins have stable overall structures at the two temperatures,further analysis indicate that they both have strong side-chain interactions anddifferent backbone flexibility at the different temperatures. The tteRBP375K andecRBP329K have stronger internal motion and higher flexibility than tteRBP300Kand ecRBP300K, respectively, it is noted that the flexibility of tteRBP is muchhigher than that of ecRBP at the two temperatures. Therefore tteRBP375K can adaptto high temperature due to its higher flexibility of backbone. Combining with theresearches by Cuneo et al.(BMC Structural Biology,2008), it is concluded that theside-chain interactions and flexibility of backbone are both the key factors to maintainthermal stability of the two proteins.2.(108Metâ†'108Leu) affected interactions between the Arabinose-Binding Proteinand ligandMolecular dynamics simulations for extremely thermophilic proteinThermoanaerobacter tengcongensis ribose binding protein(tteRBP) were performed toinvestigate the thermophilic mechanism of the protein. The comparative analysis of molecular trajectories of room temperature (300K) and optimal activity temperature(375K) show that the protein conformations are stably maintained, but the concertedmotions are different. The flexibility of the protein at375K significantly increases, sothe protein can adjust the local conformation to adapt to extreme temperature. Theanalysis of the changes in protein structure confirmed the local conformationadjustment at375K play a key role on the extreme high temperature stability.3. Molecular dynamics simulations investigate the long-range effects on TrpR andits mutantThe previous study found that when the residues75(leucine: L) were substituted byphenylalanine (F) in the tryptophan repressor protein (TrpR), this mutation conferslong-range effects on the dynamics of the protein with relatively minor effects on itsfunction. But which residues play important role in the long-range effects and if thetwo mutational residues75(each one of the two subunit) have the same effect in thelong-range effects are both unclear. So the molecular dynamics (MD) simulations andanisotropic thermal diffusion dynamics (ATD) simulations were performed on theTrpR, DTrpR (TrpR-DNA) and their mutant (mTrpR, mDTrpR) to investigate theabove questions. The ATD simulation trajectories show that during the signalingtransduction process, the mutant protein has higher extent than that of the wild, andmTrpR helix chain II F has particular disorder, the wild and mutant proteins have notthe same signaling transduction process. The wild and mutant proteins have differenttwo residues75side chain on the size and dimensional structure. So relative to thewild protein, the differences of the mutant residues75will spread to the most of theprotein by way of the signaling transduction process which have differences betweenthe wild and mutant protein. Then these will affect the protein side chain interaction,conformational changes, flexibilities and secondary structures. The MD simulationresults also show that the wild and mutant proteins have obvious differences in theprotein side chain interaction, conformational changes, flexibilities and secondarystructures. These conclusions are consistent with the previous experimental results.The wild and mutant protein residues75affect the dynamics of the protein by thelong-range effects; the mutant protein which has higher signaling transduction process has more effects. Moreover, the ATD simulations also show that each residue75ofthe symmetric homodimer has the same effect, and the two residues75have a positivecorrelation in the signaling transmission processes; the residues nearby chain I48,50,71,79and chain II45,72,80of the wild and mutant protein play important role in thesignaling transmission processes.