In particular, the consensus scoring procedure improves prediction of binding energies, which is the greatest problem in virtual screening. EPZ-6438 price Although the obtained binding energy predictions are still inaccurate and further development

is required before they can be used for this purpose in routine lead optimization, the consensus scoring procedure is at present the only alternative for improvement of the in silico screening procedure. Wang & Wang (2001) distinguished three main ranking methods of consensus scoring for virtual screening: rank-by-number (all the candidates are ranked according to the average predicted values given by all the scoring functions), rank-by-rank (all the candidates are ranked by the average ranks predicted by all the involved scoring functions) and rank-by-vote (if a candidate is predicted to be on the top, for example 2%, by a certain scoring function,

then it gets a ‘vote’ from that scoring function; the final score of a candidate compound is the number of votes gathered from all the scoring functions, which may range from 0 to the total number of scoring functions). see more The approach we applied may be treated as a modification of rank-by-number method, as we used a sum of total score by Surflex and a doubled value of fit obtained with the Screen Library module of discovery studio 2.1. Although most of the proposed hits are characterized by lipophilicity <2 (the range for CNS active drugs is from 2 to 4) and do not cross blood–brain barrier easily, it is obvious that they should be treated as prototypes of drugs that require further optimization (especially of their ADMET properties) before reaching the market. The studies performed allowed 15 potential inhibitors to be selected from the database of 1 161 000 compounds, which constitutes the reasonable alternative for experimental HTS procedure. Moreover, novel structural features of JEV NS3 helicase/NTPase have been identified,

including new important residues in the enzyme-binding pocket. The problem of anti-JEV specificity of novel compounds and their selectivity over human ATPases was also addressed. To conclude, the computational project performed may be treated as a guide for experimental very work on viral helicases/NTPases and antiviral drug design. Calculations were performed under a computational grant by the Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw, Poland, grant number G30-18. “
“T-cell help is essential for CTL-memory formation. Nevertheless, it is unclear whether the continuous presence of CD4+ T-helper (Th) cells is required during dendritic cell (DC)/CD8+ T-cell encounters, or whether a DC will remember the helper signal after the Th cell has departed. This question is relevant for the design of therapeutic cancer vaccines. Therefore, we investigated how human DCs need to interact with CD4+ T cells to mediate efficient repetitive CTL expansion in vitro.