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Cytochrome P450 reductase (CYPOR) undergoes a large conformational change to allow for an electron transfer to a redox partner to take place. After an internal electron transfer over its cofactors, it opens up to facilitate the interaction and electron transfer with a cytochrome P450. The open conformation appears difficult to crystallize. Therefore, a model of a human CYPOR in the open conformation was constructed to be able to investigate the stability and conformational change of this protein by means of molecular dynamics simulations. Since the role of the protein is to provide electrons to a redox partner, the interactions with cytochrome P450 2D6 (2D6) were investigated and a possible complex structure is suggested. Additionally, electron pathway calculations with a newly written program were performed to investigate which amino acids relay the electrons from the FMN cofactor of CYPOR to the HEME of 2D6. Several possible interacting amino acids in the complex, as well as a possible electron transfer pathway were identified and open the way for further investigation by site directed mutagenesis studies., (© 2013 The Protein Society.)

Actin is a highly conserved cytoskeletal protein that is present in all eukaryotes. Polymerization of actin to filamentous actin is essential for numerous cellular processes. Abnormal actin dynamics are directly associated with a variety of diseases, including cancer, immunological and neurological disorders. However, the dynamics of actin are not fully understood. In this work, we study the effects of nucleotides and metal ions on conformation of F/G-actin using molecular dynamics (MD) simulations. Our results show that different nucleotides and metal ions change the conformation of actin. The state of Adenosine Triphosphate (ATP) binding on F-actin conformation is more stable than G-actin. The D-loop has a large fluctuation when Ca 2 + binds to G-ATP-actin than Mg 2 + binds. Adenosine Diphosphate (ADP) binding leads to a stronger residual correlation on F-actin conformation, while it is opposite on G-actin. In addition, the detailed interactions between nucleotides and adjacent residues are discussed on different states of actin. This work provides a structural basis for understanding how the different nucleotides/metal ions binding influences the conformation of actin. Actin is crucial for cellular processes through its polymerization. Abnormal actin dynamics are linked to diseases, including cancer. This study investigates how nucleotides and metal ions impact F/G-actin conformation, providing a structural basis for understanding their influence on actin dynamics. [ABSTRACT FROM AUTHOR]

Bisphosphonate (BP) has been widely used as a bone-targeting group, and the BP-modified platinum(II) complexes have shown potential to as anticancer drugs against bone-related diseases, such as osteosarcoma. DNA conformation changes induced by the BP-modified dinuclear platinum(II) complexes have been investigated using molecular dynamics simulations. The results indicated that the BP-modified dinuclear platinum(II) complexes coordinated to DNA results in DNA structural distortions, including twisting, unwinding and bending. Furthermore, the rigidity of the bridging linkers in the BP-modified platinum(II) complex may induce more significant DNA structural distortions with same spans. The results provide the detail information of DNA conformational changes induced by the BP-modified platinum(II) complexes with different flexibility of bridging linkers, and are helpful for exploring novel platinum-based antitumor drugs. Molecular dynamics simulation of binding of dinuclear platinum(II) complexes with the bisphosphonate group to DNA is shown to cause DNA structural distortions. [Display omitted] • Molecular dynamics simulation of three dinuclear platinum(II) complexes bound to DNA are reported • Major changes to sugar pucker, groove parameter, conformation dynamics of DNA are observed • More significant DNA structural distortions are caused by the Pt(II) complexes with rigid linker [ABSTRACT FROM AUTHOR]

Dense-phase carbon dioxide (DPCD) can induce myosin denaturation and aggregation and result in the formation of a gel. To explore the mechanism that DPCD induce myosin the formation of gels, molecular dynamics simulations were used to investigate the effects of DPCD on the structural properties of the myosin heavy chain (MHC, GenBank Accession No: BAM65721.1 ) from Litopenaeus vannamei. In addition, the interaction between the MHC and CO 2 was explored under the coupling of pressure and temperature. To facilitate a better understanding and comparison, the structure of MHC was simulated in water at 0.1 MPa and 50 °C (called the myosin-water system, MWS) and in water and DPCD at 25 MPa and 50 °C (called the myosin-water-DPCD system, MWDS). The analysis of the root-mean-square deviation ( RMSD ) and root-mean-square fluctuation ( RMSF ) revealed that the conformation of the MHC in both MWDS and MWS changed significantly relative to its initial structure. Moreover, the results of the solvent-accessible surface area demonstrated that the MHC structure changes from a compact arrangement to a looser arrangement in both MWDS and MWS. Finally, the results from investigations into the secondary structures showed that the α-helix content of the MHC decreased, whereas the β-turn and random coil content increased. Greater overall structural variations of the MHC were observed in MWDS than those observed in MWS. DPCD exerts a substantial effect on the MHC structure because of its hydrogen bonding, electrostatic repulsion and hydrophobic interactions with the MHC. [ABSTRACT FROM AUTHOR]

• Lubricant conformation changes and energy transfer of confined lubricant thin films are studied by molecular dynamics simulations. • The thickness of lubricant thin film shows a power exponential relationship with pressure loads. • The lubricant thin film behaves like the Couette flow under low pressure loads, while boundary slip and temperature jump occur when high pressure loads is used. • Polymers adjusted the film conformation through a "one-step" or "two-step" mode under different loads. The lubrication system plays an important role in the reliability of moving links for spacecrafts while lubrication failure has emerged as one of the challenges in developing advanced spacecrafts with long life and high reliability. However, the process and mechanism of lubrication in space are still unclear due to a complex environment. In this study, the lubrication behavior under various pressure loads was studied by analyzing the lubricant conformation changes and energy transfer through molecular dynamics simulations. Results indicated that a "one-step" or "two-step" adjustment in the polymer conformations occurred, and the film exhibited different motion modes and temperature fields under different pressure loads. This work studied polymer thin film lubricant via energy transfer and molecular motion at a molecular level and gave a fundamental understanding on the lubrication behavior and lubrication failure of polymer thin film in space, providing theoretical guidance in developing advanced space lubrication technology. [ABSTRACT FROM AUTHOR]