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

Influence of elevated temperature on mechanical properties and durability of concrete

Concrete structures are exposed to high temperatures during fire. Bothe the mechanical properties and durability after exposed to elevated temperatures are of great importance in terms of the serviceability of buildings. In this project, the effects of elevated temperatures (20, 100, 200, 300, 400, 500 and 600 ℃ ) on the compressive strength, elastic modulus, fracture energy, water capillary absorption and chloride penetration have been studied. The influence of cooling methods on these properties has been also investigated. The results obtained indicate that when the temperature is below 400 ℃ for concrete A (W/C=0.4) and 300 ℃ for concrete B (W/C=0.5) with natural cooling, the compressive strength did not decrease immediately. But with water splashing cooling, the compressive strength of concrete lost approx. 20 % at 300 degree. The elastic modulus of concrete decreased gradually with the increasing of temperature. And there is no real difference between two types of cooling methods. When the temperature is over 400 degree only, the fracture energy decreased significantly. After exposed to elevated temperatures, concrete absorbed much more water and chloride ions, which bring a high risk for RC structures. This effect shall also be taken into consideration when concrete structures after fire is evaluated

Research of the wrinkling elimination of stainless steel SUS304 by viscous pressure

Wrinkling is one of the most important factors influencing a forming precision of sheet metal, which brings difficulties to the forming process of sheet metal. In order to eliminate the wrinkling during the forming process, an accurate prediction is necessary. In this paper, the wrinkling elimination process was investigated based on the principle of the Yoshida Buckling Test (YBT) and viscous pressure forming. The experimental device was designed, and evaluation method of the wrinkling elimination rate was presented by the stainless steel SUS304. On this basis, the wrinkling elimination experiment was carried out, the influences of both the viscous medium molecular weight and the tensile state of wrinkle under the viscous pressure on the wrinkling elimination were obtained