Design in silico

Synthetic constraints—such as difficulty, yield, management of starting materials, and intermediates—will naturally restrict the diversity of compounds that are made [7]. In silico designs with scaffolds that utilize similar synthetic steps will naturally be favored over those that are not. These pressures to make a small number of compounds with limited scaffold variability require computational methods to make exquisitely accurate predictions The... 

Even as the computational prediction error rate is reduced to acceptable levels, many cases will be encountered in which the predictions are indistinguishable to within error. In a scenario in which several different in silico designs are given equivalent but favorable activity predictions, the end user s medicinal experience may help decide which to promote to synthesis. The quality of that decision at this point will be strongly influenced by how easy it is to understand the different contributions to the computational predictions. Interpretability is thus critical for synergistically utilizing the experience of the end user. 

Molecular design has enjoyed a long history, from the preliminary trial-and-error stage to the contemporary computer-aided molecular modeling stage. In this chapter, the latter, in silico design, for nuclear applications is focused on and reviewed. 

ISIDA In Silico Design and Data Analysis Project, http //infochim.u-strasbg.fr/recher-che/isida/index.php. 

Varnek, A., Fourches, D., Solov ev, V.P. et al. 2004. In Silico design of new uranyl extractants based on phosphoryl-containing podands QSPR studies, generation and screening of virtual combinatorial library and experimental tests. J. Chem. Inf. Comput. Sci. 44 (4) 1365-1382. 

Theoretical ( in silico ) design of compounds possessing the desired properties is an ultimate objective of modeling. In chemoinformatics, it involves several stages, shown in Figure 5.12. The sets of carefully selected experimental data (1) are used... 

It is only by developing this rigorous foundation, that in silico design can progress in a rational way. 

The contribution of in silico models to vaccine development comprises algorithms for accelerated in silico identification of relevant protein candidates in silico design of novel immunogens with improved expression, safety, and immunogenicity profiles and in silico design of nucleic acid-based, vectored, or live attenuated vaccines. In small molecule development, in silico models play a major role in comparative genomics, whole genome analysis,... 

This section considers the application of fragment descriptors at different stages of virtual screening and in silico design. 

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