Many proteins use a long channel to guide the substrate or ligand molecules into the well-defined active sites for catalytic reactions or for switching molecular states. In addition, substrates of membrane transporters can migrate to another side of cellular compartment by means of certain selective mechanisms. SLITHER (http://bioinfo.mc.ntu.edu.tw/slither/or http://slither.rcas.sinica.edu.tw/) is a web server that can generate contiguous conformations of a molecule along a curved tunnel inside a protein, and the binding free energy profile along the predicted channel pathway. SLITHER adopts an iterative docking scheme, which combines with a puddle-skimming procedure, i.e. repeatedly elevating the potential energies of the identified global minima, thereby determines the contiguous binding modes of substrates inside the protein. In contrast to some programs that are widely used to determine the geometric dimensions in the ion channels, SLITHER can be applied to predict whether a substrate molecule can crawl through an inner channel or a half-channel of proteins across surmountable energy barriers. Besides, SLITHER also provides the list of the pore-facing residues, which can be directly compared with many genetic diseases. Finally, the adjacent binding poses determined by SLITHER can also be used for fragment-based drug design.

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Semibatch reactive distillation (SBRD) is a variation on batch reactive distillation (BRD) in which one reactant or an entrainer is fed to the process continuously during the batch. Qi and Malone (Qi, W; Malone, M. F. Semibatch Reactive Distillation for Isopropyl Acetate Synthesis. Ind. Eng. Chem. Res. 2011Res. , 50, 1272Res. −1277 suggested SBRD for the synthesis of isopropyl acetate with acetic acid fed continuously at the top of the column to reduce the composition of the alcohol in the distillate product. The distillate product from the SBRD is a mixture of water and ester which can subsequently be separated by inverted batch distillation (IBD). The optimization of such a two-step batch process involves trade-offs between the two steps (SBRD and IBD). In this work, an algorithm for systematic design of such processes is developed and applied to processes for the synthesis of isopropyl acetate and ethyl acetate. The key variable connecting the two batch steps is the composition of alcohol in the SBRD distillate product. Allowing a higher alcohol composition makes SBRD operation easier but IBD operation more difficult. The algorithm identifies the alcohol concentration which minimizes total process time, which is closely related to energy consumption, as well as side feed flow rate and reflux ratio profiles during the batches.

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