On Correlation Effect of the Van-der-Waals and Intramolecular Forces for the Nucleotide Chain - Metallic Nanoparticles - Carbon Nanotube Binding.

BACKGROUND: The tertiary system of nucleotide chain (NC) - gold nanoparticles (NPs) - carbon nanotube (CNT) represents a great interest in the modern research and application of the bio-nano-technologies. The application aspects include, for example, the development of electronic mobile diagnostic facilities, nanorobotic design for a drug delivery inside living cell, and so on. The small NC chain represents an important stage in the understanding of the interaction mechanism of a full DNA or RNA molecule with NP and CNT. In this regard, one has to mention the development of the DNA-CNT devices for the purposes of diagnostic applications in the chemical or drug delivery. METHODS: For the NC-NP-CNT system, we have built up a series of the molecular dynamics (MD) models with different NC-NP configurations and performed their MD analysis. The entire system (the NC chain, gold NPs and CNT) was allowed to interact with each other by the only VdW forces. The Lennard-Jones short-ranged interaction was assumed between the NC, NP and CNT. For the CNT a many body Tersoff potential having a quantum-chemistry nature was used. So far, the so-called hybrid MD approach was realized, where the quantum-chemistry potential in combination with a classical trajectory calculation applied . RESULTS: The peculiarities of the NC-NP interaction and bond formation inside of a CNT matrix were investigated along with the structural and dynamical behavior. The correlation effects between the weak Van der Waals (VdW) forces and intramolecular vibrations were enlighten for the molecular system consisting of a small nucleotide chain (NC), gold nanoparticles (NPs) and carbon nanotube (CNT) using molecular dynamics (MD) simulation method. CONCLUSION: The NC intermolecular motions were estimated from MD data thereby building the distance distributions, the angular and dihedral (torsional) bond energy graphs versus simulation time at different temperatures from T=100 K up to 300 K. The MD simulation results have shown that depending on the relative NC-NP position a different scenario of bonding between the NC-NP, within CNT matrix, is possible. We have observed the possibilities of formation of weak, strong and intermediate bonds between the NP-NC, which are overestimated by a presence of CNT matrix as confined environment. The NC chain can form with a particular gold atom a close contact, while with another under the same positional and temperature conditions the weak resultant bonding formation might be possible. We estimated the fluctuations in the NP-NC bonding processes for a single gold atomic case (models 1-3, NC-1NP-CNT), for the two (model 4-6, NC-2NP-CNT) and three (model 7, NC-3NP-CNT) gold particle ones. Thus, a concurrent effect between the NC intramolecular vibrations and a weak VdW interaction between the NC and gold NP were studied in detail.

[Simulation of Mutant P32T Homo- and Heterodimers of Human Inosine Triphosphate Pyrophosphatase hITPA].

The structure of three forms of a dimeric enzyme, human inosine triphosphate pyrophosphatase, is considered to identify the enzyme conformation changes causing the inactivation effect of a P32T mutation. Analysis of a nanosecond molecular dynamics is performed; the mean square deviations of the atoms between the wild-type and mutant homodimers, and also the heterodimer are calculated. A 3 ns modeling shows a greater displacement of atoms in mutant protomers. During molecular dynamics simulation, the strongest changes are observed in the loop between α2 and ß2 (amino acid residues 28-33, an area of the P32T mutation), the loop between ß5 and ß6, and the C-terminal amino acid residues. The loop between (α2 and ß2 has two conformations characterized by different positions of the Phe31 aromatic group. The distance between Cys33 (Cα) and Phe31 (C(z)) for wild-type and mutant protomers was -9 and 5.5 Å, respectively. These conformations were kept constant.

A Novel Approach to Simulate a Charge Transfer in DNA Repair by an Anacystis nidulans Photolyase.

An Anacystis nidulans photolyase enzyme containing two chromophore cofactors was simulated for a photoreaction DNA repairing process via molecular dynamics (MD) method. A novel approach has been introduced for the electron transfer between the FAD (flavin adenine dinucleotide; flavin) molecule and CPD (cyclobutane pyrimidine dimer). This approach involves four simulation stages with different charges for the FAD and CPD fragments and a role of a charged state of the active cofactor was qualified during the MD modeling. Observations show that flavin has actively participated in a charge transfer process, thereby involving the conformational changes of the DNA and CPD substrate fragment. The DNA conformation behavior has shown to correlate with the electron transfer from flavin to CPD. This is manifested on the similarities of the DNA repairing process by excision repair of the UV photoproducts.

[Studies on the conformational state of the chromophore group (11-cis-retinal) in rhodopsin by computer molecular simulation methods].

Based on computer simulation methods, the molecular dynamics of the rhodopsin chromophore group (11-cis-retinal) has been analyzed. The molecular dynamics has been traced within a 3-ns time interval; thereby 3 x 10(6) discrete conformational states of opsin and rhodopsin were compared and analyzed. It was shown that, within a short time of about 0.3-0.4 ns from the start of simulation, the retinal beta-ionone ring becomes twisted around the C6-C7 bond by approximately 60 degrees compared with that of the initial configuration. The influence of retinal conformation on the positions of the maximum of the absorption band of rhodopsin at the conformational states of t=0 and t=3 ns were estimated using the ab initio methods. The results indicated that the absorption maximum for the final (3-ns) state is shifted by 10 nm toward the long wavelength region compared with the initial state. This suggests that the rhodopsin molecule with its twisted chromophore will possess a considerably lower activation energy than the rhodopsin molecule where the beta-ionone ring is in a planar orientation to the retinal polyene chain.

[Simulation of kinase CDK2-cyclin A by the molecular dynamics method: effect of Gly16-->Ser16 and Arg274-->Gln274 substitutions on conformation of a kinase subunit].

The nanosecond-long molecular dynamics of the movement of the active protein kinase CDK2/ATP complex has been analyzed. The simulations of substitutions CDK2-G16S in the conserved G-loop of a small lobe and CDK2-R274Q in a large lobe showed the importance of the amino acid residues in the conformation of kinase and their effect on the conformation of CDK2, which shows up in an increase in the distance between G- and T-loops in the corresponding mutant forms. The results obtained indicate that the induction of both Gly16-->Ser16 and Arg274-->Gln274 mutations destabilize the local structure of kinase around the T-loop area. The mutation Arg274-->Gln274 has a more pronounced effect and results in a loosening of the structure of kinase and an increase of the distance between G- and T-loops.

Molecular dynamics of rhodopsin and free opsin: computer simulation.

Computer simulation was used to perform a comparative study of the molecular dynamics of rhodopsin containing the chromophore group (11-cis-retinal) and free opsin. The molecular dynamics were followed over a time interval of 3000 psec; a total of 3 x 10(6) discrete conformational states of rhodopsin and opsin. The presence of the chromophore group in the chromophore center of opsin was shown to have significant effects on the immediate protein environment of the chromophore and the conformational state of the cytoplasmic domain, but to have virtually no effect on the conformational state of the intradisk domain. The simulation results are used to discuss the possible intramolecular mechanism by which rhodopsin is maintained as a G-protein-coupled receptor in the inactive state, i.e., the function of the chromophore as an effective antagonist ligand.

[Molecular dynamics modeling of the substitution of serine for the conservative glycine in the G loop in the yeast cdc28-srm mutant using the crystalline lattice of human kinase CDK2].

Two-nanosecond molecular dynamics modeling of the crystalline lattice of an active complex of kinase pT160-CDK2/cyclin A/ATP-Mg2+ substrate has been performed. The results of modeling indicated that the structures of the nonmutant CDK2 complex and mutant CDK2 complex, which involves the G 16S-CD K2 substitution corresponding to that of yeast, markedly differ, the differences in structural conformations being particularly well pronounced in those regions that play a key role in the functioning of kinase. Based on the results of computations, structural elements are considered that may affect the kinase activity and regulatory phosphorylation, and the binding of protein kinase to cyclins and substrates.