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in silico assays amp screening for drug binding
>> YOUR LINK HERE: ___ http://youtube.com/watch?v=9-wLZpSgOrg
directory of Chem Help ASAP videos: https://www.chemhelpasap.com/youtube/ • Performing an in silico binding assay, which is a test for on-target binding through a computer simulation, requires a 3D structure of the drug target. How do you generate a 3D structure of a target? There are two main ways. One approach is to crystallize your target protein and determine a structure through x-ray crystallography. An x-ray structure gives a target model with the three-dimensional coordinates of atoms in the target. Many targets cannot be crystallized. In that case, you may be able to use a technique called homology modeling. A homology model is generated by estimating the target structure through comparisons to known proteins with known 3D structures. Models from the homology approach are less certain but sometimes are the only option. • Once you have a model, you can begin your docking experiment. Docking is the process of estimating interactions between a target and a ligand. Docking requires specialized software to perform the simulation. During docking, multiple poses or orientations of the ligand molecule binding to the target will be tested. Each pose is scored to predict drug-target binding, from which a Kd value can be estimated. So, an in silico binding assay is a computer modeled binding assay to estimate Kd values for drug-target complex. • What are some good and bad things about in silico testing? First, you absolutely need a structural model of your target. The docking software needs a structure of the target. Of course, that means you need to know what your target is, so it’s limited to target-based programs. Second, docking is extremely quick, and you can estimate the binding of many molecules very quickly. Third, and this is a major concern, the estimated Kd value will only be as good as the target structure. So, if the x-ray structure or homology model is not representative of the target structure in a cell, then your binding estimates will not be accurate or informative. Fourth and related to the previous item, the in silico predictions must be validated through experimental assays. Finally, if you are able to validate the in silico results through an experimental method, then screening molecules through an in silico assay can greatly accelerate the progress of a drug discovery program. In silico screening can not only help with identifying early active molecules but also lead selection and even lead optimization. When the potential issues can be addressed, in silico testing can be exceptionally useful.
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