In silico assessments

Costa MA, Collins RE, Anterola AM, Cochrane FC, Davin LB. 2003. An in silico assessment of gene function and organization of the phenylpropanoid pathway metabolic networks in Arabidopsis thaliana and limitations thereof. Phytochemistry 64 1097-112... 

Fig. 8.2f-h), in good agreement with the de-wetting analysis. The dehydron matrix is precisely the representational tool that enables the simplest and fastest in silico assessment of drug cross-reactivity across the entire human kinome, as described in Chap. 9. 

Many of the more recent publications on in-silico assessments of CYP interactions employ non-linear approaches. They are well suited to be applied in cases were the model interpretability is less of an issue. In fhe same venue, classification models have been developed. Although coarse-grained, these models can be used as one of a number of filters fo pick fhe mosf inferesfing compounds for subsequent experimental profiling. These classification models may also be a way to overcome the problem of noisy dafa, which are nof reliable enough for fhe generation of a quantitative model [68-83,136]. 

Bujara, M. and Panke, S. (2012) In silico assessment of cell-free systems. Biotechnol, Bioeng, 109, 2620-2629. 

Sobarzo-Sanchez, E., Bilbao-Ramos, P., Dea-Ayuela, M., Gonzalez-Diaz, H., Yanez, M., Uriarte, E., Santana, L., Martinez-Semmidez, V., Bolas-Femandez, F. Ubeira, F. M. (2013). Synthetic Oxoisoaporphine Alkaloids In Vitro, In Vivo and In Silico Assessment of Antileishmanial Activities. Plos One, 5(10), e77560. 

Trenor B, Gomis-Tena J, Cardona K et al (2013) In silico assessment of drug safety in human heart applied to late sodium current blockers. Channels (Austin) 7 249-262 Valerio LG Jr, Balakrishnan S, Fiszman ML et al (2013) Development of cardiac safety translational tools for QT prolongation and torsade de pointes. Expert Opin Drug Metab Toxicol 9 801-815... 

At the beginning of miniaturized screening study, the polymer candidates are selected based on their physicochemical properties and in-silico assessment of drug-poiymer interaction. The selected polymers are then evaluated in miniaturized screening experiments using the methods described in Sect. 5.3 for the ASD formation. 

Thus, the virtual heart may be used to simulate cardiac pathologies, their effect on the ECG, and the consequences of drug administration. It can be seen that drug discovery and assessment will be among the first fields where in silico technologies could reform research and development in a whole industry. 

New, interactive in silico teaching and educational tools will be available for doctors and the greater public. This will help to improve professional skills and general health awareness. Future health-related implications of an individual s behavioural patterns or of various treatment strategies can be assessed and compared on the basis of long-term case predictions. 

The need to decrease costs and reduce animal suffering for chemical risk assessment has ever more encouraged the use of methods alternative to the use of animals to predict toxicity. These alternative methods can be generally divided into two subgroups study of toxicity in laboratory tubes on small organisms (in vitro) and computational techniques (in silico). 

The use of computational techniques to predict toxicity, or in silico approaches, aims to decrease costs and reduce animal suffering for chemical risk assessment. 

The second step when determining impacts is the hazard assessment [28]. During the hazard assessment, the impact caused by the exposure to a substance is determined [30]. This is often done using in vitro or in silico testing. The results of the hazard assessment are often presented as dose-response functions. 

Encouraged by recent legislations all over the world aimed to protect human health and environment, alternative methods have proved their abilities to assess the toxicity of chemicals. Hence, a possible solution to the characterization of the toxicological and ecotoxicological risk of the chemicals could be represented by the application of in silico and in vitro techniques. 

Although the pressure to screen large numbers of compounds quickly has led to the rapid development of in silico and in vitro assays, the sheer number and complexity of the processes involved in determining the disposition of any particular compound means that in vivo studies are still required to provide assurance that the important processes are modeled with sufficient accuracy [4-6], and indeed, that the potential contribution of processes for which there are no good in vitro models (e.g., biliary secretion) are adequately assessed. 

The aim of the present example was to investigate whether the assessment of an in silico model of metabolic stability from a training set of several hundred drugs or drug-like compounds in human CYP3A4 cDNA-expressed microsomal preparations, would offer a suitable approach to predict the metabolic stability of external compounds. 

The large majority of the studies undertaken to understand druggability from an assessment of either in vitro and or in silico physicochemical properties are aimed at the common goal of ameliorating the risk of... 

Fig. 8. Reconstruction of Young s modulus map in a simulated object. A 3D breast phantom was first designed in silico from MR anatomical images. Then a given 3D Young s modulus distribution was supposed with a 1 cm diameter stiff inclusion of 200 kPa (A). The forward problem was the computing of the 3D-displacement field using the partial differential equation [Eq. (5)]. The efficiency of the 3D reconstruction (inverse problem) of the mechanical properties from the 3D strain data corrupted with 15% added noise can be assessed in (B). The stiff inclusion is detected by the reconstruction algorithm, but its calculated Young s modulus is about 130 kPa instead of 200 kPa. From Ref. 44, reprinted by permission of Wiley-Liss, Inc., a subsidiary of John Wiley Sons, Inc.

Horvath, D. and Jeandenans, C. (2003) Neighborhood behavior of in silico structural spaces with respect to in vitro activity spaces - a benchmark for neighborhood behavior assessment of different in silico similarity metrics. Journal of Chemical Information and Computer Sciences, 43, 691-698. 

Jacobs, M.N. (2004) In silico tools to aid risk assessment of endocrine disrupting chemicals. Toxicology, 205, 43—53. 

N. Jamshidi, S. J. Wiback, and B. 0. Palsson, In silico model driven assessment of the effects of single nucleotide polymorphisms (SNPs) on human red blood cell metabolism. Gen. Res. 12 (11), 1687 1692 (2002). 

From the above we conclude that in silico absorption models are very useful tools in assessing the development potential of compounds in the drug discovery process, and their use in discovery projects could help to reduce the attrition rate due to poor pharmacokinetic properties in later phases. The... 

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