CSAR scoring challenge reveals the need for new concepts in estimating protein-ligand binding affinity

The dG prediction accuracy by the Lead Finder docking software on the CSAR test set was characterized by R(2)=0.62 and rmsd=1.93 kcal/mol, and the method of preparation of the full-atom structures of the test set did not significantly affect the resulting accuracy of predictions. The primary factors determining the correlation between the predicted and experimental values were the van der Waals interactions and solvation effects. Those two factors alone accounted for R(2)=0.50. The other factors that affected the accuracy of predictions, listed in the order of decreasing importance, were the change of ligand's internal energy upon binding with protein, the electrostatic interactions, and the hydrogen bonds. It appears that those latter factors contributed to the independence of the prediction results from the method of full-atom structure preparation. Then, we turned our attention to the other factors that could potentially improve the scoring function in order to raise the accuracy of the dG prediction. It turned out that the ligand-centric factors, including Mw, cLogP, PSA, etc. or protein-centric factors, such as the functional class of protein, did not improve the prediction accuracy. Following that, we explored if the weak molecular interactions such as X-H...Ar, X-H...Hal, CO...Hal, C-H...X, stacking and π-cationic interactions (where X is N or O), that are generally of interest to the medicinal chemists despite their lack of proper molecular mechanical parametrization, could improve dG prediction. Our analysis revealed that out of these new interactions only CO...Hal is statistically significant for dG predictions using Lead FInder scoring function. Accounting for the CO...Hal interaction resulted in the reduction of the rmsd from 2.19 to 0.69 kcal/mol for the corresponding structures. The other weak interaction factors were not statistically significant and therefore irrelevant to the accuracy of dG prediction. On the basis of our findings from our participation in the CSAR scoring challenge we conclude that a significant increase of accuracy predictions necessitates breakthrough scoring approaches. We anticipate that the explicit accounting for water molecules, protein flexibility, and a more thermodynamically accurate method of dG calculation rather than single point energy calculation may lead to such breakthroughs.     

Epoxy polymers based on functional adamantane derivatives

The main routes for modification of epoxy polymers with functional adamantane derivatives consisting of four saturated cycles are considered. It is shown that the high thermodynamic stability and rigidity of adamantane structure define a complex of properties of epoxy polymers and materials, as compared to the known polymers based on acyclic epoxy resins.     

Three-coloring statistical model with domain wall boundary conditions: Functional equations

We consider the Baxter three-coloring model with boundary conditions of the domain wall type. In this case, it can be proved that the partition function satisfies some functional equations similar to the functional equations satisfied by the partition function of the six-vertex model for a special value of the crossing parameter.     

Optical Adhesives Based on Phosphorus-containing Epoxy Polymers

The refractive indices, transmission coefficients, and other service characteristics of binary and amine-cured mixtures epoxy oligomer-glycidyl esters of phosphorus acids, proposed as optical adhesives, were measured.     

Thermally enhanced response of metal—oxide—metal diodes

It is shown that in thin-film MOM diodes of contact area ~ 2.5 × 10^-9 m² the basic mechanism of infrared and visible laser radiation detection is the tunneling current dependence on contact temperature (thermally enhanced tunneling). Experiments were run on Al—Al₂O₃—Al MOM diodes.     

Vector nonlinear interactions of light waves in LiIO3 and K2S2O6 crystals

The influence of the physical properties of crystals on the noncollinear interaction of light waves in nonlinear media is examined in an example of LiIO₃ and K₂S₂O₆. Peculiarities in the vector interaction are noted in crystals with quadratic and cubic nonlinearities. Experimental results are presented.Translated from Izvestiya Vysshikh Uchebnykh Zavedenii, Fizika, No. 8, pp. 65–70, August, 1974.     

Correlation of millimeter-band radio-wave attenuation in cloud and rain parts of cloud-rain system

The experimentally detected difference by a factor of two or more of the autocorrelation times of millimeter-wave attenuation in the rain and cloud parts of a cloud-rain system is examined. In cases of moderate to heavy rain, the measured autocorrelation time of millimeter-wave attenuation in the cloud part of the system is greater by a factor of two than that in the rain for a given degree of cloudiness. In the case of drizzle, the measured relationship is inverted: the attenuation autocorrelation time in the rain part exceeds that in the cloud part by a factor of two. Specific realizations are used; the problem of estimation of the average correlation-time relationships, which is required for prolonged measurement periods, is not posed; nevertheless, the need for its formulation follows from the results considered here. The physical meaning of the results is that the horizontal spatial heterogeneities of moderate to heavy rain are smaller than those of drizzle and greater than those of the clouds from which the given rain falls.Scientific-Research Radio-Physics Institute. Translated from Izvestiya Vysshikh Uchebnykh Zavedenii, Radiofizika, Vol. 36, No. 3–4, pp. 231–239, March–April, 1993.     

Finite Size XXZ Spin Chain with Anisotropy Parameter Δ= \frac{1} {2}

We find an analytic solution of the Bethe–Ansatz equations (BAE) for the special case of a finite XXZ spin chain with free boundary conditions and with a complex surface field which provides for U_q(sl(2)) symmetry of the Hamiltonian. More precisely, we find one nontrivial solution, corresponding to the ground state of the system with anisotropy parameter Δ= $\frac{1}{2}$ corresponding to q³=?1. With a view to establishing an exact representation of the ground state of the finite size XXZ spin chain in terms of elementary functions, we concentrate on the crossing parameter η dependence around η=π/3 for which there is a known solution. The approach taken involves the use of a physical solution Q of Baxter's T-Q equation, corresponding to the ground state, as well as a non-physical solution P of the same equation. The calculation of P and then of the ground state derivative is covered. Possible applications of this derivative to the theory of percolation have yet to be investigated. As far as the finite XXZ spin chain with periodic boundary conditions is concerned, we find a similar solution for an assymetric case which corresponds to the 6-vertex model with a special magnetic field. For this case we find the analytic value of the “magnetic moment” of the system in the corresponding state.