Intrinsically disordered proteins or intrinsically disordered protein regions comprise a large portion of eukaryotic proteomes (between 35% and 51%). These intrinsically disordered proteins were found to link with cancer and various other diseases. However, widely used additive force field parameter sets are insufficient in quantifying the structural properties of intrinsically disordered proteins. Therefore, we explored to a systematic correction of a base additive force field parameter set (chosen as Amber ff99SBildn) to correct the biases that was first demonstrated in simulations with the base parameter set. Specifically, the φ/ψ distributions of disorder-promoting residues were systematically corrected with the CMAP method. Our simulations show that the CMAP corrected Amber parameter set, termed ff99IDPs, improves the φ/ψ distributions of the disorder-promoting residues with respect to the benchmark data of intrinsically disordered protein structures, with root mean-squared percentage deviation less than 0.15% between the simulation and the benchmark. Our further validation shows that the chemical shifts from the ff99IDPs simulations are in quantitative agreement with those from reported NMR measurements for two tested IDPs, MeV NTAIL , and p53. The predicted residue dipolar couplings also show high correlation with experimental data. Interestingly, our simulations show that ff99IDPs can still be used to model the ordered state when the intrinsically disordered proteins are in complex, in contrast to ff99SBildn that can be applied well only to the ordered complex structures. These findings confirm that the newly proposed Amber ff99IDPs parameter set provides a reasonable tool in further studies of intrinsically disordered protein structures. In addition, our study also shows the importance of considering intrinsically disordered protein structures in general-purposed force field developments for both additive and non-additive models.

We theoretically demonstrate the mechanically mediated electromagnetically induced transparency in a two-mode cavity optomechanical system, where two cavity modes are coupled to a common mechanical resonator. When the two cavity modes are driven on their respective red sidebands by two pump beams, a transparency window appears in the probe transmission spectrum due to destructive interference. Under this situation the transmitted probe beam can be delayed as much as 4 µs, which can be easily controlled by the power of the pump beams. In addition, we also investigate the amplification of the transmitted probe beam owing to constructive interference when one cavity is driven on its blue sideband while another one is driven on its red sideband.

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Directional amplifiers are crucial nonreciprocal devices in both classical and quantum information processing. Here we propose a scheme for realizing a directional amplifier between optical and microwave fields based on an optomechanical system with optical gain, where an active optical cavity and two passive microwave cavities are, respectively, coupled to a common mechanical resonator via radiation pressure. The two passive cavities are coupled via hopping interaction to facilitate the directional amplification between the active and passive cavities. We obtain the condition of achieving optical directional amplification and find that the direction of amplification can be controlled by the phase differences between the effective optomechanical couplings. The effects of the gain rate of the active cavity and the effective coupling strengths on the maximum gain of the amplifier are discussed. We show that the noise added to this amplifier can be greatly suppressed in the large cooperativity limit.

Lac repressor is a DNA-binding protein which inhibits the expression of a series of genes involved in lactose metabolism. Lac repressor can bind at a random DNA site via nonspecific interactions; then, it rapidly translocates through the double chain of DNA until it finds the specific binding site. Therefore, the site transform between these two modes is essential for the specific recognition between Lac repressor and DNA. Here, the recognition mechanism between Lac repressor and DNA was illustrated with molecular dynamics simulations and correlation network analyses. We have found that the correlation network of the specific system (2KEI) is more centralized and denser than that of the nonspecific system (1OSL). The significant difference in the networks between the nonspecific and specific systems is apparently due to the different binding modes. Then, different interaction modes were found where electrostatic and hydrogen bonding interactions in the nonspecific system are stronger than those in the specific system. Hydrophobic interactions were found only in specific complexes and mostly focused on the hinge helices. Furthermore, the hinge helix will induce the bending of DNA for the specific system. At the same time, a common specific sequence of DNA was revealed for three specific systems. Then, two design systems (positive and control) were used to evaluate the specific recognition between DNA and Lac repressor. These combined methods can be used to reveal the recognition mechanism between other transcription factors and DNA.

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Antibody-antigen specific recognition is essential in autoimmunity. In this study, antibody SPE7 binding to protein antigens and to hapten molecules were carefully analyzed in order to gain insight into their binding mechanisms. X-ray crystal structures show that SPE7 can adopt at least four different conformations, as in the two observed free isomers (Ab(1) and Ab(2)) and the two observed bound conformers (Ab(3) and Ab(4)). Multidimensional scaling analysis reveals that antibody SPE7 may obey a global conformational selection mechanism upon its binding to an antigen. The conformations of key residue at the binding site (Trp93L) further reveals that bound isomer Ab(3) may come from free isomer Ab(2), and bound isomer Ab(4) from free isomer Ab(1). The average root-mean-square deviation (RMSD) values between the bound isomers and the corresponding free isomers and Kolmogorov-Smimov P test analysis indicate that the antibody may also follow a local induced fit mechanism at the binding interface. Quantitative analysis indicates that the magnitude of the local induced fit interaction at the binding site is more pronounced than that of the global conformational selection interaction. These conclusions are further supported by high-temperature unbinding kinetics analysis. The computational methods proposed here can also be used to study the specific recognitions between other antibody and antigen systems.

We explore theoretically the bistable behavior of intracavity photon number in a two-mode cavity optomechanical system, where two cavity modes are coupled to a common mechanical resonator. When the two cavity modes are driven by two pump laser beams, respectively, we find that the optical bistability can be controlled by tuning the power and frequency of the pump beams. The common interaction to a mechanical mode enables one to control the bistable behavior in one cavity by adjusting the pump laser beam driving another cavity. We also show that both branches of optical bistability at photon numbers below unity can be observed in this two-mode optomechanical system. This phenomenon can find potential applications in controllable optical switch.