A knowledge-guided strategy for improving the accuracy of scoring functions in binding affinity prediction

<p>Abstract</p> <p>Background</p> <p>Current scoring functions are not very successful in protein-ligand binding affinity prediction albeit their popularity in structure-based drug designs. Here, we propose a general knowledge-guided scoring (KGS) strategy to tackle this problem. Our KGS strategy computes the binding constant of a given protein-ligand complex based on the known binding constant of an appropriate reference complex. A good training set that includes a sufficient number of protein-ligand complexes with known binding data needs to be supplied for finding the reference complex. The reference complex is required to share a similar pattern of key protein-ligand interactions to that of the complex of interest. Thus, some uncertain factors in protein-ligand binding may cancel out, resulting in a more accurate prediction of absolute binding constants.</p> <p>Results</p> <p>In our study, an automatic algorithm was developed for summarizing key protein-ligand interactions as a pharmacophore model and identifying the reference complex with a maximal similarity to the query complex. Our KGS strategy was evaluated in combination with two scoring functions (X-Score and PLP) on three test sets, containing 112 HIV protease complexes, 44 carbonic anhydrase complexes, and 73 trypsin complexes, respectively. Our results obtained on crystal structures as well as computer-generated docking poses indicated that application of the KGS strategy produced more accurate predictions especially when X-Score or PLP alone did not perform well.</p> <p>Conclusions</p> <p>Compared to other targeted scoring functions, our KGS strategy does not require any re-parameterization or modification on current scoring methods, and its application is not tied to certain systems. The effectiveness of our KGS strategy is in theory proportional to the ever-increasing knowledge of experimental protein-ligand binding data. Our KGS strategy may serve as a more practical remedy for current scoring functions to improve their accuracy in binding affinity prediction.</p

Boundary effect and dressed states of a giant atom in a topological waveguide

The interaction between the quantum emitter and topological photonic system makes the photon behave in exotic ways. We here study the properties of a giant atom coupled to two sites of a one-dimensional topological waveguide, which is described by the Su-Schrieffer-Heeger (SSH) chain. We find that the giant atom can act as an effective boundary and induce the chiral zero modes, which are similar to those in the SSH model with open boundary, for the waveguide under the periodical boundary. Except for the boundary effect, we also find that the giant atom can lift energy degeneracy inside the energy bands of the SSH chain and adjust spatial symmetry of the photon distributions for the states of the dressed giant atom and waveguide. That is, the giant atom can be used to change the properties of the topological environment. Our work may stimulate more studies on the interaction between matter and topological environment.Comment: 7 Pages, 4 Figure

Quantum interference and controllable magic cavity QED via giant atom in coupled resonator waveguide

We study the Markovian and Non-Markovian dynamics in a giant atom system which couples to a coupled resonator waveguide (CRW) via two distant sites. Under certain conditions, we find that the giant atom population can exhibit an oscillating behavior and the photon can be trapped in the giant atom regime. These phenomena are induced by the interference effect among the bound states both in and outside the continuum. As an application of the photon trapping, we theoretically propose a magic cavity model where the giant atom serve as either a perfect or leaky cavity, depending on the distance between the coupling sites. The controllability of the magic cavity from perfect to leaky one can not be realized in the traditional cavity or circuit QED setup. The predicted effects can be probed in state-of-the-art waveguide QED experiments and provide a striking example of how the different kinds of bound states modify the dynamics of quantum open system in a structured environment.Comment: 11 pages, 7 figures, comments are welcome

Witness of topological phase transition and Weyl points in an open topological system

Recently, the tunable Weyl-semimetal bands and the associate topological phase transition have been successfully simulated in superconducting quantum circuits [X. Tan, \textit{et al.} Phys. Rev. Lett. {\bf 122}, 010501 (2019)]. Since the superconducting quantum circuits inevitably couple to the environment, we here focus on the steady state and decoherence process by taking the reservoir into consideration via quantum master equation. Our results show that the purity of the steady state can be used to indicate the topological phase transition and Weyl points. Furthermore, the coherence will exponentially decay to zero at the Weyl points, and decay to a nonzero value with oscillation at other points in the momentum space. Our work may have significant impact on the study of quantum open topological system.Comment: 5 pages, 4 figure

Effects of temperature on photosynthetic performance and nitrate reductase activity in vivo assay in Gracilariopsis lemaneiformis (Rhodophyta)

Gracilariopsis lemaneiformis is an economically-valued species and widely cultured in China at present. After being acclimated to different growth temperatures (15, 20, 25, and 30 degrees C) for 7 days, the relative growth rate (RGR), nitrate reductase activity, soluble protein content and chlorophyll a fluorescence of G. lemaneiformis were examined. Results show that RGR was markedly affected by temperature especially at 20 degrees C at which G. lemaneiformis exhibited the highest effective quantum yield of PSII [Y(II)] and light-saturated electron transport rate (ETRmax), but the lowest non-photochemical quenching. Irrespective of growth temperature, the nitrate reductase activity increased with the incubation temperature from 15 to 30 degrees C. In addition, the greatest nitrate reductase activity was found in the thalli grown at 20 degrees C. The value of temperature coefficient Q10 of alga cultured in 15 degrees C was the greatest among those of other temperatures tested. Results indicate that the optimum temperature for nitrate reductase synthesis was relatively lower than that for nitrate reductase activity, and the relationship among growth, photosynthesis, and nitrate reductase activity showed that the optimum temperature for activity of nitrate reductase in vivo assay should be the same to the optimal growth temperature

Analysis of a whole-space transient electromagnetic field in 2.5-dimensional FDTD geoelectric modeling

Mine water inrush poses a serious threat to the safe production of coal mines in China. The transient electromagnetic method (TEM) on the ground has been applied to explore water-bearing structures, but the resolution is low. Therefore, some geophysicists in China moved the TEM onto underground coal mine roadways and obtained good results at the end of the last century. Although the TEM has been applied in mining for many years, there are so few theoretical studies that the data interpretation is not accurate. It is necessary to study the transient electromagnetic eld diffusion in the entire space with physical or numerical simulation methods. First, based on the diffusion equations, we deduced the wave number domain equations, whose whole-space electromagnetic eld is excited by a 3-D source in a 2-D geoelectric model; then, we derived the 2.5-D nite-difference time domain equations. At the beginning of the calculation, we gave the grid nodes near the source the initial values with the cosine ltering method. To improve the calculating ef ciency, the time intervals gradually increased with time. At the end of the calculation, we transformed the calculating results from the wave number domain to the space domain by tting the segmented exponential function. Compared with the analytical solutions, the numerical solutions are accurate, and the algorithm is reliable and ef cient. The simulation results of a collapse-column model show that the transient electromagnetic eld diffusion in the entire space is dominated by low-resistivity bodies.This work was supported in part by the Major State Basic Research Development Program of China(973 Program) under Grant 2013CB227900, in part by the National Natural Science Foundation of China under Grant 41304113, in part by the China Scholarship Council under Grant 201606425004, and in part by the National Research Foundation, South Africa under Grant IFR160118156967 and Grant RDYR160404161474.http://ieeexplore.ieee.org/xpl/RecentIssue.jsp?punumber=6287639am2017Electrical, Electronic and Computer Engineerin

Molecular insights into functional differences between mcr-3- and mcr-1-mediated colistin resistance

The global emergence of plasmid-mediated colistin resistance genes mcr-1 and mcr-3 has threatened the role of the “last resort” drug colistin in the defense against infections caused by multidrug-resistant Gram-negative bacteria. However, functional differences between these two genes in mediating colistin resistance remains poorly understood. Protein sequence alignment of MCR-3 and MCR-1 was therefore conducted in Clustal Omega to identify sequence divergence. The molecular recognition of lipid A head group phosphatidylethanolamine and MCR-3 enzyme was studied by homology modeling and molecular docking, with the catalytic mechanism of MCR-3 also being explored. Thr277 in MCR-3 was validated as the key amino acid residue responsible for the catalytic reaction using site-directed mutagenesis and was shown to act as a nucleophile. Lipid A modification induced by the MCR-3 and MCR-1 enzymes was confirmed by electrospray ionization time-of-flight mass spectrometry. Far-UV circular dichroism spectra of the MCR-3 and MCR-1 enzymes suggested that MCR-3 was more thermostable than MCR-1, with a melting temperature of 66.19°C compared with 61.14°C for MCR-1. These data provided molecular insight into the functional differences between mcr-3 and mcr-1 in conferring colistin resistance