Reverse virtual screening

In our recent studies we were fortunate to recruit experimental collaborators who have validated computational hits identified by virtual screening of commercially available compound libraries using rigorously validated QSAR models. Examples include anticonvulsants (25), HIV-1 reverse transcriptase inhibitors (32), D1 antagonists (33), antitumor compounds (34), beta-lactamase inhibitors (35), human histone deacetylase (HDAC) inhibitors... 

Scholkopf B, Platt JC, Shawe-Taylor J, Smola AJ, Williamson RC (2001) Estimating the support of a high-dimensional distribution. Neural Comput 13(7) 1443-1471 Karpov PV, Baskin II, Zhokhova NI, Zefirov NS (2011) Method of continuous molecular fields in the one-class classification task. Dokl Chem 440(2) 263-265 Karpov PV, Baskin II, ZhokhovaNI,Nawrozkij MB, ZefirovAN, Yablokov AS, Novakov lA, Zefirov NS (2011) One-class approach models for virtual screening of non-nucleoside HIV-1 reverse transcriptase inhibitors based on the concept of continuous molecular fields. Russ Chem Bull 60(ll) 2418-2424. doi 10.1007/slll72-011-0372-8... 

The interaction modes applied within virtual environments in the historical context of human communication are not new. In fact, the tendency to limit communication to screen and keyboard, driven during the last decades by computer technology, will be reversed and communication wiU be shifted back to a human standard. 

For dissociation reactions in which the reverse, recombination step is slow, dissociation is virtually complete once the pair has separated to the contact distance. Under these conditions the magnitude of the interaction in the dissociated pair, in particular the screening of this interaction by ions, would not affect the dissociation rate. In terms of the Hammond postulate [22] and its extensions [23] an exothermic dissociation process would have its transition state close to the bound state, so that the equilibrium and recombination rate coefficients would change in parallel. In such a case one expects no salt effect on the dissociation reaction, in agreement with the classical picture of Bronsted and Bjerrum for kinetic salt effects [7]. 

Because of the physical construction of a tetrode, the control grid will have virtually no control over screen-to-plate current flow as a result of secondary electrons. During a portion of the operating cycle of the device, it is possible that more electrons wiU leave the screen grid than will arrive. The result will be a reverse electron flow on the screen element, a condition common to high-power tetrodes. A low-impedance path for reverse electron flow must be provided. 

In addition to the product-ion scan, most MS-MS instruments allow other scan modes, e.g. neutral-loss and precursor-ion scan modes. The modes are not only useful in the elucidation of the fragmentation pattern of a particular compound, but also in the screening for a series of structurally-related compounds in complex samples. In the product-ion scan mode, the first mass analyser selects a particular precursor ion, while the product ions obtained by CID of this precursor are analysed in the second mass analyser. In the precursor-ion scan mode, this process is virtually reversed the first mass analyser transmits all ions in a preset mIz window to the collision cell, while the second analyser selects only the ions of one particular miz, e.g. a particular structure informative fragment for a series of ions or compounds. An example of the use of the precursor-ion scan mode is the monitoring of phthalate plasticisers by means of the common fragment ion at miz 149 due to protonated phthalic anhydride. In the neutral-loss scan modes, both mass analysers are... 

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